ABSTRACT
BACKGROUND: Reducing postprandial hyperglycemia and hypoglycemia is a major challenge in the treatment of patients with diabetes. Studies suggest that heating the insulin injection site may accelerate insulin absorption. InsuPatch (InsuLine Medical Ltd., Petach-Tikva, Israel) is a device intended to accelerate subcutaneous insulin delivery using an insulin pump by locally warming the infusion site. OBJECTIVE: The aim of this study was to assess the effect of the InsuPatch device on the pharmacokinetics of short-acting insulin analogues and on postprandial glycemia. METHODS: This was an open-label, randomized, 2-period, 1-way crossover study using a meal tolerance test (MTT) protocol in subjects with type 1 diabetes mellitus aged 18 to 65 years with glycosylated hemoglobin (HbA(1c)) of 6% to 12%, who were using continuous subcutaneous insulin infusion (CSII) therapy (insulin lispro or aspart). A bolus of insulin 0.15 U/kg was delivered immediately before a standardized liquid meal. The effect of the device on insulin absorption and postprandial glucose excursions was tested by measuring blood glucose and insulin concentration profiles with and without the operation of the device. Adverse events (AEs) were monitored during the 2 study visits. The infusion site was visually inspected at the end of each study. All AEs were recorded in the case-report form. RESULTS: The MTT protocol was performed in 17 white patients with type 1 diabetes (sex, male/female, 7/10; mean age, 31.8 years [range, 18-53 years]; mean body mass index, 25.6 kg/m(2) [range, 20.0-39.4 kg/m(2)]; and mean HbA(1c), 7.1% [range, 5.8%-9.3%]). The mean (SD) postprandial glucose excursion AUC at 120 minutes after the meal was significantly reduced in the group that used the device compared with the group that did not (104 [65] vs 155 [56] mg/dL/h; P < 0.005). Plasma insulin was measured randomly in 9 of the 17 subjects. Use of the device was associated with significant reductions in mean (SD) T(max) (45 [28] vs 78 [35] minutes) and time to half-maximum concentration (T(50%max)) (20 [11] vs 28 [10] minutes; both, P < 0.05). Insulin AUC increased significantly in the group that used the device compared with the group that did not at 30 (21 [6] vs 33 [16] mU/L/h), 60 (55 [12] vs 80 [28] mU/L/h), and 90 (93 [19] vs 118 [31] mU/L/h) minutes after administration (all, P < 0.05). Cmax also increased significantly (118 [35] vs 86 [16] mU/L [38%]; P < 0.05). CONCLUSION: In this pilot study, use of the InsuPatch was associated with significant decreases in T(max) and T(50%max) and increases in insulin AUC and C(max) of subcutaneous infused rapid-acting insulin analogues, resulting in a lower postprandial glucose excursion in these patients with type 1 diabetes mellitus treated with CSII.
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Equipment and Supplies , Glucose/pharmacokinetics , Hot Temperature/therapeutic use , Insulin Infusion Systems , Insulin/administration & dosage , Insulin/pharmacokinetics , Adolescent , Adult , Aged , Area Under Curve , Blood Glucose/drug effects , Cross-Over Studies , Female , Humans , Infusions, Subcutaneous , Insulin/blood , Male , Middle Aged , Pilot Projects , Young AdultABSTRACT
BACKGROUND: In type 1 diabetes (T1D), closed-loop systems provide excellent overnight fasting blood glucose control by adjusting the insulin infusion rate based on corresponding changes in sensor glucose levels. In patients on multiple daily insulin (MDI) injections, such control in overnight glucose levels has not been possible due to the inability to alter the absorption rate of long-acting insulin after injection. In this study, we tested the hypothesis that increases/decreases of fasting glucose levels could be achieved by cooling/warming the skin around the injection site, which would result in lower/higher Glargine absorption rates from its subcutaneous depot. METHODS: Fourteen subjects with T1D (4 females; age 39.6 ± 16.7 years, HbA1c 7.8 ± 1.1%, BMI 25.4 ± 2.8 kg/m2) on MDI therapy underwent fasting pharmacokinetic and pharmacodynamic studies that started at ~8 am and lasted 240 min on 3 separate days in random order: a control day without warming or cooling of the injection site and two experimental days, one day with injection site warming and the other with cooling. RESULTS: Cooling the skin around the glargine injection site reduced insulin concentrations by >40% (P < .01 versus the warming study, P = .21 versus the control study), accompanied by a 55 mg/dL increase in serum glucose (P < .01 versus the control study). Conversely, skin warming prevented the fall in serum insulin (P = .2 versus the control study; P < .01 versus the cooling study), resulting in a 40 mg/dL reduction in serum glucose (P < .001 versus the cooling study, P = .11 versus the control study). CONCLUSIONS: This proof of concept study has shown that cooling and warming the skin around the injection site provides a means to decrease and increase the rate of absorption and action of insulin glargine from its subcutaneous depot.
Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/pharmacology , Insulin Glargine/pharmacology , Skin Temperature/physiology , Adult , Cold Temperature , Cross-Over Studies , Diabetes Mellitus, Type 1/blood , Female , Glycated Hemoglobin/analysis , Hot Temperature , Humans , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/therapeutic use , Insulin Glargine/pharmacokinetics , Insulin Glargine/therapeutic use , Male , Middle Aged , Young AdultABSTRACT
Emerging nanotechnologies hold great promise for creating new means of detecting pollutants, cleaning polluted waste streams, and recovering materials before they become wastes, thereby protecting environmental quality. Studies focusing on the different advantages of nanoscience and nanotechnology abound in the literature, but less research effort seems to be directed toward studying the fate and potential impacts of wastes that will be generated by this technology. Using a combination of biogeochemical and toxicological methods, we conducted a preliminary investigation of the potential environmental fate of Hg as an example pollutant bound to nanomaterials used in treatment of gas effluents. Methylation of Hg sorbed onto SiO(2)-TiO(2) nanocomposites was used as a proxy for Hg bioavailability to sedimentary microorganisms, and the FluoroMetPLATE assay was used to assess the toxicity of both virgin and Hg-loaded SiO(2)-TiO(2) nanocomposites. Our results show that the bioavailability of Hg sorbed onto SiO(2)-TiO(2) nanocomposites to sedimentary microorganisms is pH dependent, with decreasing reaction rates as the pH increases from 4 to 6. Toxicity tests conducted using liquid extracts obtained by leaching of Hg-loaded SiO(2)-TiO(2) nanocomposites with the synthetic precipitation leaching procedure solution showed an average inhibition of 84% (vs 57% for virgin SiO(2)-TiO(2) nanocomposites). These results suggest that Hg sorbed onto engineered nanoparticles could become bioavailable and toxic if introduced into natural systems. Accordingly, studies focusing on the environmental implications of nanomaterials should include determination of the fate and impacts of pollutants that enter the environment bound to engineered nanomaterials.
Subject(s)
Environmental Pollutants/chemistry , Mercury/chemistry , Nanocomposites/chemistry , Adsorption , Hydrogen-Ion Concentration , Methylation , Nanocomposites/toxicity , Waste ManagementABSTRACT
The aim of the present work is the assessment of metal toxicity in runoff, in their contaminated soils and in the groundwater sampled from two mining areas in the region of Marrakech using a microbial bioassay MetPLATE. This bioassay is based on the specific inhibition of the beta-galactosidase enzyme of a mutant strain of Escherichia coli, by the metallic pollutants. The stream waters from all sampling stations in the two mines were all very toxic and displayed percent enzyme inhibition exceeding 87% except SWA4 and SWB1 stations in mine C. Their high concentrations of copper (Cu) and zinc (Zn) confirm the acute toxicity shown by MetPLATE. The pH of stream waters from mine B and C varied between 2.1 and 6.2 and was probably responsible for metal mobilization, suggesting a problem of acid mine drainage in these mining areas. The bioassay MetPLATE was also applied to mine tailings and to soils contaminated by the acidic waters. The results show that the high toxicity of these soils and tailings was mainly due to the relatively concentration of soluble Zn and Cu. The use of MetPLATE in groundwater toxicity testing shows that, most of the samples exhibited low metal toxicity (2.7-45.5% inhibition) except GW3 of the mine B (95.3% inhibition during the wet season and 82.9% inhibition during the dry season). This high toxicity is attributed to the higher than usual concentrations of Cu (189 microg Cu l(-1)) and Zn (1505 microg Zn l(-1)). These results show the potential risk of the contamination of different ecosystems situated to the vicinity of these two metalliferous sites. The general trend observed was an increase in metal toxicity measured by the MetPLATE with increasing total and mobile metal concentrations in the studied matrices. Therefore, the MetPLATE bioassay is a reliable and fast bioassay to estimate the metals toxicity in the aquatic and solids samples.
Subject(s)
Biological Assay/methods , Industrial Waste/analysis , Metals, Heavy , Mining , Soil Pollutants , Water Pollutants, Chemical , Environmental Monitoring , Humans , Metals, Heavy/analysis , Metals, Heavy/toxicity , Morocco , Rivers/chemistry , Soil Pollutants/analysis , Soil Pollutants/toxicity , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicityABSTRACT
Our work was conducted to investigate the heavy metal toxicity of tailings and soils collected from five metal mines located in the south of Morocco. We used the MetPAD biotest Kit which detects the toxicity specifically due to the heavy metals in environmental samples. This biotest initially developed to assess the toxicity of aquatic samples was adapted to the heterogeneous physico-chemical conditions of anthropogenic soils. Contrasted industrial soils were collected from four abandoned mines (A, B, C and E) and one mine (D) still active. The toxicity test was run concurrently with chemical analyses on the aqueous extracts of tailings materials and soils in order to assess the potential availability of heavy metals. Soil pH was variable, ranging from very acidic (pH 2.6) to alkaline values (pH 8.0-8.8). The tailings from polymetallic mines (B and D) contained very high concentrations of Zn (38,000-108,000 mg kg(-1)), Pb (20,412-30,100 mg kg(-1)), Cu (2,019-8,635 mg kg(-1)) and Cd (148-228 mg kg(-1)). Water-extractable metal concentrations (i.e., soil extracts) were much lower but were highly toxic as shown by the MetPAD test, except for soils from mines A, E and site C3 from mine C. The soil extracts from mine D were the most toxic amongst all the soils tested. On this site, the toxicity of soil water extracts was mainly due to high concentrations of Zn (785-1,753 mg l(-1)), Cu (1.8-82 mg l(-1)) and Cd (2.0-2.7 mg l(-1)). The general trend observed was an increase in metal toxicity measured by the biotest with increasing available metal contents in tailings materials and soils. Therefore, the MetPAD test can be used as a rapid and sensitive predictive tool to assess the heavy metal availability in soils highly contaminated by mining activities.
Subject(s)
Metals, Heavy/analysis , Mining , Soil Pollutants/analysis , Hydrogen-Ion Concentration/drug effects , Metals, Heavy/toxicity , Morocco , Soil Pollutants/toxicityABSTRACT
Metalliferous soils cover a relatively large surface area in Morocco, and up to now no hyperaccumulating plants have been identified on these mining or these industrial sites. The aim of this work was to assess the extent of metal accumulation by plants found in three mining areas in southern Morocco with the ultimate goal of finding metal hyperaccumulating species by using the MetPAD biotest. The biotest helps to obtain information on the selective metal toxicity of aqueous extracts from the plants. A strong metal toxicity, as revealed by the biotest is an indication of a hyperaccumulating plant. Toxicity tests were run concurrently with chemicals analyses of metals in plants and their water extracts. The chemical analyses allow the determination of the hyperaccumulated metal(s). Specimens of the plant species mainly growing on and in the vicinity of the three mines were sampled with their corresponding soils. The results show that all plants analyzed had lower heavy metal content and toxicity despite the relatively very high soil concentrations. A comparison of our results with the criterion used to classify the hyperaccumulator plants indicates that plants we collected from mining sites were hypertolerant but not hyperaccumulators. This was confirmed by transfer factors generally lower than 1. Nevertheless, these tolerant plants species can be used as tools for revegetation for erosion control in metals-contaminated sites (phytostabilization).
Subject(s)
Metals, Heavy/analysis , Mining , Plants/chemistry , Soil Pollutants/analysis , Metals, Heavy/toxicity , Morocco , Plants/drug effects , Soil Pollutants/toxicityABSTRACT
Hydrogen sulfide (H2S) generation in construction and demolition (C&D) debris landfills has been associated with the biodegradation of gypsum drywall. Laboratory research was conducted to observe H2S generation when drywall was codisposed with different C&D debris constituents. Two experiments were conducted using simulated landfill columns. Experiment 1 consisted of various combinations of drywall, wood, and concrete to determine the impact of different waste constituents and combinations on H2S generation. Experiment 2 was designed to examine the effect of concrete on H2S generation and migration. The results indicate that decaying drywall, even alone, leached enough sulfate ions and organic matter for sulfate-reducing bacteria (SRB) to generate large H2S concentrations as high as 63,000 ppmv. The codisposed wastes show some effect on H2S generation. At the end of experiment 1, the wood/drywall and drywall alone columns possessed H2S concentrations > 40,000 ppmv. Conversely, H2S concentrations were < 1 ppmv in those columns containing concrete. Concrete plays a role in decreasing H2S by increasing pH out of the range for SRB growth and by reacting with H2S. This study also showed that wood lowered H2S concentrations initially by decreasing leachate pH values. Based on the results, two possible control mechanisms to mitigate H2S generation in C&D debris landfills are suggested.
Subject(s)
Air Pollutants, Occupational/analysis , Construction Materials , Hydrogen Sulfide/analysis , Industrial Waste , Refuse Disposal , Computer Simulation , Environmental Monitoring , Hydrogen Sulfide/chemistry , Models, StatisticalABSTRACT
The biological conversion of sulfate from disposed gypsum drywall to hydrogen sulfide (H(2)S) in the anaerobic environment of a landfill results in odor problems and possible health concerns at many disposal facilities. To examine the extent and magnitude of such emissions, landfill gas samples from wells, soil vapor samples from the interface of the waste and cover soil, and ambient air samples, were collected from 10 construction and demolition (C&D) debris landfills in Florida and analyzed for H(2)S and other reduced sulfur compounds (RSC). H(2)S was detected in the well gas and soil vapor at all 10 sites. The concentrations in the ambient air above the surface of the landfill were much lower than those observed in the soil vapor, and no direct correlation was observed between the two sampling locations. Methyl mercaptan and carbonyl sulfide were the most frequently observed other RSC, though they occurred at smaller concentrations than H(2)S. This research confirmed the presence of H(2)S at C&D debris landfills. High concentrations of H(2)S may be a concern for employees working on the landfill site. These results indicate that workers should use proper personal protection at C&D debris landfills when involved in excavation, landfill gas collection, or confined spaces. The results indicate that H(2)S is sufficiently diluted in the atmosphere to not commonly pose acute health impacts for these landfill workers in normal working conditions. H(2)S concentrations were extremely variable with measurements occurring over a very large range (from less than 3 ppbv to 12,000 ppmv in the soil vapor and from less than 3 ppbv to 50 ppmv in ambient air). Possible reasons for the large intra- and inter-site variability observed include waste and soil heterogeneities, impact of weather conditions, and different site management practices.
Subject(s)
Air Pollutants/analysis , Construction Materials , Refuse Disposal , Sulfur Compounds/analysis , Environmental Monitoring , Florida , Gases/analysis , OdorantsABSTRACT
The study reported here looked at the survival of microorganisms (heterotrophic plate counts, total coliforms, E. coli, and bacterial spores) in a consumer-type microwave oven. Kitchen sponges, scrubbing pads, and syringes were experimentally contaminated with wastewater and subsequently exposed to microwave radiation. At 100 percent power level, it was found that the heterotrophic plate count (i.e., total bacterial count) of the wastewater was reduced by more that 99 percent within 1 to 2 minutes, and the total coliform and E. coli were totally inactivated after 30 seconds of microwave radiation. Bacterial phage MS2 was totally inactivated within 1 to 2 minutes. Spores of Bacillus cereus were more resistant than the other microorganisms tested, and were completely eradicated only after 4-minute irradiation. Similar inactivation rates were obtained in wastewater-contaminated scrubbing pads. Microorganisms attached to plastic syringes were more resistant to microwave irradiation than those associated with kitchen sponges or scrubbing pads. It took 10 minutes for total inactivation of the heterotrophic plate count and 4 minutes for total inactivation of total coliform and E. coli. A 4-log reduction of phage MS2 was obtained after 2 minutes; 97.4 percent reduction was observed after 12 minutes. The authors also observed a higher inactivation of B. cereus spores in syringes placed in a ceramic container than of spores in syringes placed in a glass container. This finding could have some implications for the design of containers to be used in exposure of medical devices to microwave radiation. The article discusses the implications of these findings for consumer safety in the home environment.
Subject(s)
Bacteria/radiation effects , Food Microbiology , Household Products/microbiology , Microwaves , Bacteria/growth & development , Household Products/classification , TemperatureABSTRACT
Zero valent iron (ZVI) has been widely tested and used in remediation of both contaminated soils and groundwater, and in general, the in situ amendment of the contaminated media is used as remediation approach. However, concerns remain as to the potential detrimental effects of both the immobilized ZVI and the adsorbed pollutants as the treated system could undergo transformations over time. Accordingly, plans for soil remediation by in situ immobilization of sorbents should include a long-term monitoring of the treated systems. Here, we report on a comparative study in which artificially Cu-contaminated sandy and organic soils characterized by different metal binding capacities were treated by either (i) in situ immobilization of ZVI in the soils, or (ii) by a ZVI amendment followed by magnetic retrieval of formed ZVI-Cu complexes prior to plant growth studies. The latter relies on the combination of the high metal adsorption capacity and magnetism of ZVI. Two plant species, Lactuca sativa (lettuce) and Brassica juncea (Indian mustard) were used to assess the efficiency of the two treatment methods in eliminating the bioavailable fraction of Cu. Overall, the results showed that, if soil remediation by in situ immobilization reduces the bio-accessible fraction of Cu, treatment using ZVI amendment followed by magnetic separation performs better. The latter resulted in less Cu accumulated in the shoots and roots of plants. In parallel to the plant growth study, we used MetPLATE™, a short-term bioassay based on the inhibition of the ß-galactosidase enzyme by the bioavailable fraction of heavy metal cations, to predict the efficiency of the two treatment methods with regard to the elimination of Cu phyto-toxicity. The results of the bioassay confirmed the trends of phyto-toxicity results, suggesting that MetPLATE™ could be an adequate alternative to the more expensive, labor intensive, and time consuming plant growth studies.
Subject(s)
Copper/metabolism , Iron/metabolism , Lactuca/metabolism , Metals, Heavy/metabolism , Plant Roots/metabolism , Soil Pollutants/metabolism , Soil/chemistry , Adsorption , Biodegradation, Environmental , Environmental Pollution , Florida , Magnetic FieldsABSTRACT
This research describes the use of a toxicity assay for the identification of metal toxicity, bioavailability and heavy metal binding capacity (HMBC) of municipal solid waste (MSW) landfill leachates. MetPLATE, an assay specific for heavy metal toxicity, was used to determine the HMBC of MSW leachates collected from 14 sites in Florida, with a wide range of chemical and physical characteristics. The leachates displayed a low toxicity which was attributed to the site-specific parameters, including, high concentrations of both organic and inorganic ligands. The HMBC test was undertaken to measure the effect of these site-specific parameters on metal toxicity. The potential for MSW leachate to bind and, thus, detoxify heavy metals was investigated with copper, zinc, and mercury. The HMBC values obtained ranged from 3 to 115, 5 to 93 and 4 to 101 for HMBC-Cu+2, HMBC-Zn+2, and HMBC-Hg+2, respectively. Additionally, the high strength leachates displayed the highest binding capacities, although the landfills sampled represented a wide range of characteristics. For comparison, the HMBC values reported with local lake water, Lake Alice and Lake Beverly, and a wastewater treatment plant effluent were all below 3. A partial fractionation of MSW leachate samples from sites 1, 5 and 8, was conducted to further investigate the influence of selected site-specific physico-chemical parameters on metal binding. The fractionation revealed that the HMBC of the leachate samples was heavily influenced by the concentration of solids, organics and hardness.
Subject(s)
Metals, Heavy/metabolism , Refuse Disposal , Soil Pollutants/metabolism , Water Pollutants, Chemical/metabolism , Binding Sites , Cities , Environmental Monitoring , Florida , Fresh Water , Metals, Heavy/analysis , Toxicity TestsABSTRACT
BACKGROUND: Delays in the time-action profiles of premeal boluses of rapid-acting insulin analogs contribute to early postmeal hyperglycemia in patients with diabetes. We tested whether applying local heat to skin around the injection site to increase the rate of insulin absorption reduces postprandial hyperglycemia in patients with type 2 diabetes. METHODS: Fourteen patients with type 2 diabetes (4 females; age 61.6 ± 8.4 years, HbA1c 8.42 ± 1.13%; BMI 29.10 ± 5.61 kg/m(2)) on intensified insulin therapy underwent 5-hour meal tolerance tests (MTTs) with a standardized liquid meal after an overnight fast on 2 study days. Subjects injected 0.2 U/kg of insulin aspart or lispro subcutaneously into the abdominal skin on both days with and without the use of the InsuPad device. RESULTS: Following the premeal bolus injection of rapid-acting insulin analog, infusion site warming led to a rise in plasma insulin levels to peak concentrations that were significantly earlier than without skin warming (mean ± SD 52 ± 26.7 vs 80 ± 51.3 minutes, P < .005) as well as increase in plasma insulin levels during the first hour after injection (mean ± SD 63.5 ± 32.7 IU vs 48.0 ± 25.0 uU.min/ml, P = .019). As a result, the area under the curve of the postprandial glucose excursion during the first 2 hours (the primary study outcome) and the entire 5 hours after the meal were significantly reduced (P = .007 and P = .03, respectively) with skin warming around the injection site. DISCUSSION AND CONCLUSIONS: Use of the InsuPad to increase the rate of insulin absorption provides an effective means to achieve better control of postmeal glucose excursions in type 2 diabetic patients receiving premeal injections of rapid-acting insulin analogs.
Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 1/drug therapy , Hyperglycemia/prevention & control , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Insulin Infusion Systems , Insulin/administration & dosage , Insulin/therapeutic use , Adolescent , Adult , Aged , Cross-Over Studies , Female , Glucose Tolerance Test , Glycated Hemoglobin/analysis , Humans , Infusions, Subcutaneous , Insulin/blood , Male , Middle Aged , Temperature , Young AdultABSTRACT
Temperature changes on the surface of the skin lead to modifications of subcutaneous microcirculation. This phenomenon is employed in a standardized way by the InsuPad device to stabilize skin conditions before injections, which is associated with enhanced prandial insulin absorption. Three programmed warming cycles to 40°C within 50 minutes are resulting in faster insulin appearance in the plasma. Early standardized meal tolerance studies indicated a substantial improvement in postprandial glucose control when the same short-acting insulin analog dose was applied using InsuPad, and a dose reduction by 20% resulted in comparable glucose excursions. Similar results were obtained when patients applied the device under real-world conditions for 1 month. The InsuPad device was also tested in a prospective, controlled, parallel 3-month real-world study with 145 well-controlled but insulin-resistant patients with type 1 or type 2 diabetes. Patients were treated to target in both treatment arms (6.2 ± 0.5% in each group), with or without the device. However, patients with InsuPad needed 28% less prandial insulin, needed 12.5% less total insulin, and had 46% less confirmed hypoglycemic events (blood glucose < 63 mg/dL) as compared to the control group. Except for very few inflammatory or allergic skin reactions, there were no device-specific adverse events reported from these studies. In conclusion, use of InsuPad when applying prandial insulin doses may result in a safer and more efficient treatment of type 1 or type 2 diabetes.
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Insulin/administration & dosage , Insulin/pharmacokinetics , Subcutaneous Absorption , Blood Glucose/metabolism , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Humans , Injections, Subcutaneous/standards , Insulin/adverse effects , Meals , Postprandial Period , Randomized Controlled Trials as Topic/statistics & numerical data , Treatment OutcomeABSTRACT
The InsuPad is a medical device to accelerate insulin resorption by applying local heat at the insulin injection site. This crossover study examined the impact of the InsuPad use on postprandial glucose excursions under daily life conditions. In 1 study phase, diabetic patients used the InsuPad when injecting bolus insulin before breakfast and dinner and measured their blood glucose 5 times daily (before breakfast, lunch, and dinner and after breakfast and dinner). In the other study phase, blood glucose measurements were maintained without using the InsuPad. The order of the study phases was randomized. Twenty patients with a high insulin demand took part (30% type 1 diabetes, age 53.7 ± 8.9 years, diabetes duration 14.9 ± 7.4 years; HbA1c 8.3 ± 0.8%; total daily insulin demand 0.97 ± 0.32 IU per kg). Postprandial glucose excursion was reduced by 15.4 mg/dl (95% CI 9.7-21.2 mg/dl; P = .011) after breakfast and dinner if InsuPad was used. The mean blood glucose was lower by 8.8 mg/dl (95% CI 0:3-18:0 mg/dl; P = .099) when using the InsuPad. Safety parameters and the percentage of hypoglycemic (< 60 mg/dl) or hyperglycemic (> 300 mg/dl) blood glucose measurements were not negatively affected by InsuPad use (hypoglycemic values 1.4% vs 1.5%, P = .961; hyperglycemic values 2.6% vs 4.0%, P = .098). Local heating of the insulin injection site by use of the InsuPad device is an effective and safe method to reduce postprandial blood glucose excursions under daily life conditions without negative side effects on the occurrence of low or high blood glucose values.
Subject(s)
Blood Glucose/analysis , Heating/methods , Hyperglycemia/prevention & control , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Cross-Over Studies , Diabetes Mellitus/drug therapy , Female , Humans , Male , Middle Aged , Postprandial PeriodABSTRACT
The absorption profile of rapid-acting insulin analogs delivered subcutaneously is slow compared with physiological insulin. Shorter time to peak and shorter duration of insulin action are important steps toward reducing high postprandial blood glucose concentrations in diabetes therapy and are critical for the development of a closed-loop insulin delivery system. Many attempts have been made to develop more rapid-acting insulins. Since the 1950s, different approaches, such as jet injectors and sprinkler needles, which try to increase the absorption areas of injected insulin, have been developed; however, none of them are commonly used in diabetes therapy. Massage and heat increase tissue blood perfusion and, thereby, the absorption of subcutaneously applied insulin. The main focus of this article is a novel device that allows local application of heat to human skin. The device can be connected to a regular insulin pump. This device could demonstrate a significant effect on insulin absorption and postprandial glucose excursions in multiple clinical trials.
Subject(s)
Blood Glucose/drug effects , Hot Temperature/therapeutic use , Insulin, Short-Acting/administration & dosage , Insulin, Short-Acting/pharmacokinetics , Regional Blood Flow/physiology , Skin Temperature/physiology , Skin/blood supply , Absorption , Blood Glucose/metabolism , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacokinetics , Injections, Subcutaneous/instrumentation , Injections, Subcutaneous/methods , Insulin Infusion Systems , Models, Biological , Postprandial Period/drug effects , Skin Absorption/physiologyABSTRACT
This study investigates the biological response of Pseudokirchneriella subcapitata to single-walled carbon nanotubes (SWNTs) suspended in gum Arabic (GA), using typical 96-hour algal bioassays and long-term growth studies. Changes in algal biomass and cell morphology associated with specific SWNT-treatments were monitored and the mechanisms of observed biological responses investigated through a combination of biochemical and spectroscopic methods. Results from short-term bioassays showed a growth inhibition in culture media containing >0.5 mg SWNT/L and a final GA concentration of 0.023% (v/v). Interestingly, the observed toxicity disappears when GA concentrations are brought to levels ≥ 0.046%. Long-term experiments based on toxic combination of SWNTs and GA showed that P. subcapitata would easily recover from an initial growth inhibition effect. Overall, these findings point to the possibility of GA to mitigate the toxicity of SWNTs, making it an ideal surfactant if SWNT suspension in GA does not alter the performance sought from these nanotubes.
Subject(s)
Chlorophyta/drug effects , Gum Arabic/chemistry , Nanotubes, Carbon/toxicity , Biomass , Chlorophyta/growth & development , Nanotubes, Carbon/chemistry , Spectroscopy, Near-Infrared , Spectrum Analysis, Raman , Surface-Active Agents , Toxicity TestsABSTRACT
Disposal of gypsum drywall in landfills has been demonstrated to elevate hydrogen sulfide (H(2)S) concentrations in landfill gas, a problem with respect to odor, worker safety, and deleterious effect on gas-to-energy systems. Since H(2)S production in landfills results from biological activity, the concept of inhibiting H(2)S production through the application of chemical agents to drywall during disposal was studied. Three possible inhibition agents - sodium molybdate (Na(2)MoO(4)), ferric chloride (FeCl(3)), and hydrated lime (Ca(OH)(2)) - were evaluated using flask and column experiments. All three agents inhibited H(2)S generation, with Na(2)MoO(4) reducing H(2)S generation by interrupting the biological sulfate reduction process and Ca(OH)(2) providing an unfavorable pH for biological growth. Although FeCl(3) was intended to provide an electron acceptor for a competing group of bacteria, the mechanism found responsible for inhibiting H(2)S production in the column experiment was a reduction in pH. Application of both Na(2)MoO(4) and FeCl(3) inhibited H(2)S generation over a long period (over 180 days), but the impact of Ca(OH)(2) decreased with time as the alkalinity it contributed was neutralized by the generated H(2)S. Practical application and potential environmental implications need additional exploration.
Subject(s)
Calcium Sulfate , Hydrogen Sulfide/antagonists & inhibitors , Anaerobiosis , Hydrogen Sulfide/chemical synthesisABSTRACT
The aim of the present work is the assessment of the concentration, toxicity and phytoavailability of heavy metals in garden soils in the vicinity of three mines (A, B and C) in South of Morocco by using concurrently selective chemical extractions, MetPLATE a toxicity bioassay and plant growth experiments. The tailings materials containing very high concentrations of Mn, Cu and Co in mine A, Co, Mn, Cr and Ni in mine B and Cu and Zn in mine C. The high toxicity of tailings from mine C (86.7% inhibition) and moderate toxicity of tailings from mine B (51.0% inhibition) were mainly due to the relative high concentrations of soluble Cu and Zn. Nevertheless, the low metal toxicity observed in most garden soils was confirmed by the low metal concentrations in the soil water extracts. In all garden soils, Lactuca sativa L. and Lolium multiflorum L. contained in their shoots Cd, Co, Cr, Cu and Ni below toxic concentrations while Zn (in all soils) and Mn in two soils from mine A were accumulated at concentrations high enough to be considered phytotoxic. The low biomass produced on garden soils in the vicinity of mines B and C is explained by the relative low toxicity compared to mine A. Transfer factor values for Zn were higher than those found for Mn for both plant species, confirming that this element is present at lower bioavailable fraction in soil than Zn.
Subject(s)
Industrial Waste/analysis , Metals, Heavy/pharmacokinetics , Metals, Heavy/toxicity , Mining , Soil/analysis , Biomass , Environmental Monitoring , Morocco , Toxicity TestsABSTRACT
Experimental conditions that mimic likely scenarios of manufactured nanomaterials (MNs) introduction to aquatic systems were used to assessthe effect of nanoparticle dispersion/solubility and water chemical composition on MN-toxicity. Aqueous suspensions of fullerenes (C60), nanosilver (nAg), and nanocopper (nCu) were prepared in both deionized water and filtered (0.45 microm) natural river water samples collected from the Suwannee River basin, to emphasize differences in dissolved organic carbon (DOC) concentrations and solution ionic strengths (I). Two toxicity tests, the Ceriodaphnia dubia and MetPLATE bioassays were used. Results obtained from exposure studies show that water chemistry affects the suspension/solubility of MNs as well as the particle size distribution, resulting in a wide range of biological responses depending on the type of toxicity test used. Under experimental conditions used in this study, C60 exhibited no toxicity even when suspended concentrations exceeded 3 mg L(-1). MetPLATE results showed that the toxicity of aqueous suspensions of nCu tends to increase with increasing DOC concentrations, while increasing I reduces nCu toxicity. The use of the aquatic invertebrate C. dubia on the other hand showed a tendency for decreased mortality with increasing DOC and I. MetPLATE results for nAg showed decreasing trends in toxicity with increasing DOC concentrations and I. However, C. dubia exhibited contrasting biological responses, in that increasing DOC concentrations reduced toxicity, while the latter increased with increasing I. Overall, our results show that laboratory experiments that use DI-water and drastic MN-suspension methods may not be realistic as MN-dispersion and suspension in natural waters vary significantly with water chemistry and the reactivity of MNs.