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In a fifth aspect of the first embodiment, the sensor data from the first analyte sensor includes at least twenty sensor data points, wherein the sensor data from the second analyte sensor includes at least twenty sensor data points, and wherein calibrating the sensor data further comprises forming at least twenty matched data pairs by matching each sensor data point from the first analyte sensor to a corresponding sensor data point from the second analyte sensor and forming a calibration set comprising at least twenty matched data pairs.
In a sixth aspect of the first embodiment, the method further includes constructing a first curve from the sensor data from the first analyte sensor and constructing a second curve from the sensor data from the second analyte sensor, wherein calibrating the sensor data from the first analyte sensor comprises matching the first curve with the second curve.
In a seventh aspect of the first embodiment, the first analyte sensor is a short term substantially continuous analyte sensor and the second analyte sensor is a short term substantially continuous analyte sensor. In a eighth aspect of the first embodiment, the first analyte sensor is a long term substantially continuous analyte sensor and the second analyte sensor is a long term substantially continuous analyte sensor.
In a ninth aspect of the first embodiment, the first analyte sensor is a short term substantially continuous analyte sensor and the second analyte sensor is a long term substantially continuous analyte sensor.
In a tenth aspect of the first embodiment, the method further includes receiving data from a non-continuous reference source, and wherein said calibrating further includes using data from the non-continuous reference source to calibrate the sensor data from the second analyte sensor. In an eleventh aspect of the first embodiment, the non-continuous reference source is a blood glucose monitor. In a twelfth aspect of the first embodiment, the non-continuous reference source is an in-vitro calibration.
In a thirteenth aspect of the first embodiment, the non-continuous reference source is an optical sensor. In a fourteenth aspect of the first embodiment, calibrating the long term sensor data further includes using sensor data from the short term analyte sensor to update the calibration of the long term analyte sensor. In a second embodiment, the invention includes a method of processing data from a substantially continuous analyte sensor, the method including testing an analyte sensor prior to insertion into a host to determine at least one sensor data characteristic, employing the analyte sensor in the host, receiving sensor data from the analyte sensor, and calibrating the sensor data using the sensor data characteristic.
In one aspect of the second embodiment, the substantially continuous analyte sensor is a short term sensor. In a second aspect of the second embodiment, the substantially continuous analyte sensor is an implantable long term sensor. In a third aspect of the second embodiment, the method further includes receiving reference data from a reference analyte monitor, the reference data comprising at least one reference data characteristic and calibrating the sensor data using the reference data characteristic.
In a fourth embodiment, the invention includes a system for calibrating a substantially continuous analyte sensor, the system including a first substantially continuous analyte sensor, a second substantially continuous analyte sensor, a first sensor data receiving module operably linked to said first sensor and configured to receive at least one sensor data point from said first sensor, a second sensor data receiving module operably linked to said second sensor and configured to receive at least one sensor data point from said second sensor, and a processor module in data communication with the first sensor data receiving module linked to said first sensor and further in data communication with the second sensor data receiving module linked to said second sensor, said processor module configured to calibrate the sensor data from the first sensor using sensor data from the second sensor.
In one aspect of the fourth embodiment, the processor module is further configured to match at least one time-matched data point from said first analyte sensor and said second analyte sensor to form at least one calibration set for calibrating the first analyte sensor including at least one matched data pair. In a second aspect of the fourth embodiment, the first analyte sensor is a long term substantially continuous analyte sensor and the second analyte sensor is a short term substantially continuous analyte sensor.
In a third aspect of the fourth embodiment, the first analyte sensor is a short term substantially continuous analyte sensor and the second analyte sensor is a short term substantially continuous analyte sensor. In a fourth aspect of the fourth embodiment, the first analyte sensor is a long term substantially continuous analyte sensor and the second analyte sensor is a long term substantially continuous analyte sensor.
In a fifth aspect of the fourth embodiment, the first analyte sensor is a short term substantially continuous analyte sensor and the second analyte sensor is a long term substantially continuous analyte sensor. In a sixth aspect of the fourth embodiment, the first substantially continuous analyte sensor and said second substantially continuous analyte sensor are each glucose sensors.
In a fifth embodiment, the invention includes a method for simultaneously utilizing at least two analyte sensors, the method including receiving sensor data from a first analyte sensor, receiving sensor data from a second analyte sensor, and processing the sensor data from the first analyte sensor using the sensor data from the second analyte sensor.
In one aspect of the fifth embodiment, the sensor data from the second analyte sensor comprises time delay information and processing comprises modifying the sensor data from a first analyte sensor responsive to the time delay information. In a second aspect of the fifth embodiment, processing comprises utilizing the sensor data from the second analyte sensor to assess performance of the first analyte sensor. In a third aspect of the fifth embodiment, the first analyte sensor is a transcutaneous sensor.
In a fourth aspect of the fifth embodiment, the first analyte sensor is a wholly implantable sensor. In one embodiment of this aspect, the second analyte sensor is a transcutaneous sensor. In a fifth aspect of the fifth embodiment, the second analyte sensor is a transcutaneous sensor.
In a sixth aspect of the fifth embodiment, the second analyte sensor is a wholly implantable sensor. In a seventh aspect of the fifth embodiment, the processing comprises calibrating the first analyte sensor. The figures illustrate the system prior to and during initial and continued release of the mounting unit from the host's skin.
The following description and examples illustrate a preferred embodiment of the present invention in detail. Those of skill in the art will recognize that there are numerous variations and modifications of this invention that are encompassed by its scope. Accordingly, the description of a preferred embodiment should not be deemed to limit the scope of the present invention.
In order to facilitate an understanding of the disclosed invention, a number of terms are defined below. In some embodiments, the analyte for measurement by the sensing regions, devices, and methods is glucose.
Salts, sugar, protein, fat, vitamins and hormones naturally occurring in blood or interstitial fluids can also constitute analytes in certain embodiments. The analyte can be naturally present in the biological fluid, for example, a metabolic product, a hormone, an antigen, an antibody, and the like. The metabolic products of drugs and pharmaceutical compositions are also contemplated analytes. Analytes such as neurochemicals and other chemicals generated within the body can also be analyzed, such as, for example, ascorbic acid, uric acid, dopamine, noradrenaline, 3-methoxytyramine 3MT , 3,4-dihydroxyphenylacetic acid DOPAC , homovanillic acid HVA , 5-hydroxytryptamine 5HT , and 5-hydroxyindoleacetic acid FHIAA.
For example, some embodiments utilize a membrane that contains glucose oxidase that catalyzes the conversion of oxygen and glucose to hydrogen peroxide and gluconate: See Clarke et al.
Clinical acceptability considers a deviation between time corresponding glucose measurements e. In one example, congruence can be determined using rank correlation. The Consensus Error Grid is divided into zones signifying the degree of risk posed by the deviation. See Parkes et al. A data association function is used to show data association.
For example, the data that forms that calibration set as described herein can be analyzed mathematically to determine its correlation to, or deviation from, a curve e. A data association function is used to determine data association. In one such example, the correlation coefficient of linear regression is indicative of the amount of data association of the calibration set that forms the conversion function, and thus the quality of the calibration.
In the case of the counter electrode, a reducible species, for example, O 2 is reduced at the electrode surface in order to balance the current being generated by the working electrode. For example, a short term analyte sensor can have a lifespan of about less than about an hour to about three weeks, and a long term analyte sensor has a corresponding lifespan of longer than three weeks. For example, one or more electrodes can be used to detect the amount of analyte in a sample and convert that information into a signal; the signal can then be transmitted to an electronic circuit means.
The domain can then act as an oxygen reservoir during times of minimal oxygen need and has the capacity to provide on demand a higher oxygen gradient to facilitate oxygen transport across the membrane.
This enhances function in the enzyme reaction domain and at the counter electrode surface when glucose conversion to hydrogen peroxide in the enzyme domain consumes oxygen from the surrounding domains. Thus, this ability of the oxygen antenna domain to apply a higher flux of oxygen to critical domains when needed improves overall sensor function. For example, an R-value can be calculated for a calibration set to determine its statistical data association, wherein an R-value greater than 0.
In one example, the sensing membrane comprises an immobilized glucose oxidase enzyme, which enables an electrochemical reaction to occur to measure a concentration of glucose. In one example, a sensor head comprises a non-conductive body, a working electrode anode , a reference electrode and a counter electrode cathode passing through and secured within the body forming an electrochemically reactive surface at one location on the body and an electronic connective means at another location on the body, and a sensing membrane affixed to the body and covering the electrochemically reactive surface.
The counter electrode has a greater electrochemically reactive surface area than the working electrode. During general operation of the sensor a biological sample e.
In some embodiments, the sensing membrane further comprises an enzyme domain e. For example, a short term analyte sensor can have a lifespan of less than an hour to about three weeks, and a long term analyte sensor has a corresponding lifespan of longer than three weeks.
In the disclosure which follows, the following abbreviations apply: Some of the aspects of the invention relate to calibrating a substantially continuous analyte sensor e. The analyte sensor can be any type of sensor that measures a concentration of an analyte of interest or a substance indicative of the concentration or presence of the analyte.
The analyte sensors can be short or long term sensors. For example, in some embodiments, the sensor data from a short term substantially continuous analyte sensor is used to calibrate the sensor data from another short term substantially continuous analyte sensor. In another embodiment, the sensor data from a short term substantially continuous analyte sensor is used to calibrate the sensor data from a long term substantially continuous analyte sensor.
In one embodiment, the sensor data from a long term substantially continuous analyte sensor is used to calibrate the sensor data from another long term substantially continuous analyte sensor. In other embodiments, the sensor data from a long term substantially continuous analyte sensor is used to calibrate the sensor data from a short term substantially continuous analyte sensor.
The analyte sensors can use any method of analyte-sensing, including enzymatic, chemical, physical, electrochemical, spectrophotometric, polarimetric, calorimetric, radiometric, or the like.
The system includes two substantially continuous analyte sensors, sensor A and sensor B , configured to provide sensor data to a receiver. Sensor A and sensor B can be any substantially continuous analyte sensors capable of determining the level of an analyte in the body, for example glucose, oxygen, lactase, insulin, hormones, cholesterol, medicaments, viruses, or the like. Sensor A and sensor B can be short term or long term sensors.
Sensor A and sensor B detect information relating to an analyte in the host 6 and transmit the information e. The transmission of the sensor data can be through a wire or wireless communication channel. In this embodiment, sensor A and sensor B measure the same analyte e. In such an embodiment, the receiver is configured to receive the sensor data from both sensors, process the data, and calibrate one of the sensors, using e.
This embodiment also includes two substantially continuous analyte sensors, sensor C and sensor D , that detect information relating to an analyte in the host 6 and transmit the information to a receiver. In this embodiment, sensor C transmits sensor data to receiver A and sensor D transmits sensor data to receiver B.
Receiver A and receiver B are configured to communicate information with each other e. Here, for example, so long as the receivers can communicate, the communication protocol, content, and data format for one sensor and its receiver can be different than for the other sensor and its receiver.
Some of the embodiments described and illustrated herein, e. However, in such embodiments, additional receivers can be employed e. A long term analyte sensor can have an initial instability time period during which it is unstable for environmental, physiological, or other reasons. For example, for a long term analyte sensor implanted subcutaneously, its stabilization can be dependent upon the maturity of the tissue ingrowth around and within the sensor see, e.
Accordingly, determination of sensor stability can include waiting a time period e. In this embodiment, the short term sensor measures the analyte and provides data to a receiver during the waiting period.
Once the long term sensor is deemed to be stable, the data from the long term sensor requires calibration to provide an accurate value. Where the sensor data from the short term sensor has a correlative or predictive relationship with the sensor data from the long term sensor, the data from the short term sensor can be used to calibrate the long term sensor.
The sensor data from a long term sensor can change over time, due to, for example, a decrease in its sensitivity. In one embodiment, a long term sensor can be re-calibrated by employing a short term sensor on the same host as the long term sensor and then using the sensor data from the short term sensor to calibrate the sensor data from the long term sensor.
For example, on a host having a long term e. A short term sensor taking a measurement every five minutes provides sensor data for measurements in a day.
The receiver translates the short sensor data to estimate analyte values, which are used to re-calibrate the long term sensor using e. As another example, a short term sensor can be used to trouble shoot a long term sensor, for example, when the long term sensor is wholly implanted in the host and experiences malfunctioning. In such a situation, a short term sensor can be inserted into the host e. In certain circumstances a single short term sensor is not able to provide sensor data for the entire waiting period of the long term sensor.
For example, the lifespan of the short term sensor may be less than the requisite waiting period. Accordingly, the use of two or more short term sensors can be used to provide sensor data for the entire waiting period for a long term sensor if the waiting period is greater than three days.
For example, a short term sensor A is used to provide analyte measurements to a receiver for its usable lifespan. Prior to the end of the lifespan of sensor A, short term sensor B is employed to also provide analyte measurements to a receiver for the host 6 , so that sensor A and sensor B are both providing sensor data during an overlapping time period. If the waiting period of the long term sensor is longer than the period that can be covered by sensor A and B, another short-term sensor can be employed prior to the end of the lifespan of sensor B.
Substitution of short term sensors in an overlapping manner can be repeated until the expiration of the waiting period. Once the long term sensor is stable, it can be calibrated using sensor data from one or more of the short term sensors. Alternatively, one or more short-term sensor may be implanted near the time when the long term sensor is expected to start working rather than having the short term sensors implanted during the entire waiting period of the long term sensor.
In one embodiment, where two or more short term sensors are used on the same host, the sensor data from one short term sensor can be used to calibrate the other short term sensor. For example, in the above-described embodiment, the receiver can use the sensor data from sensor A to calibrate the sensor data from B, which can be used to calibrate each successive short term sensor employed on the host 6. In some embodiments, one or more of the short term sensors are calibrated in-vitro, e.
In such embodiments, the series of short term sensors need not overlap each other for calibration purposes. In one example, a benchtop calibrated short term sensor can be used to calibrate a long term implantable glucose sensor so that manual glucose measurements SMBG are not needed. According to one embodiment of a sensor, the sensing mechanism of an enzyme-electrode based glucose sensor depends on two phenomena that are linear with glucose concentration: Typically, calibration requires at least two independent, paired measurements x 1 , y 1 ; x 2 , y 2 to solve for m and b and thus allow glucose estimation when only the sensor signal, y is available.
In one embodiment of a semi-benchtop calibration technique, prior information e. If there exists a predictive relationship between benchtop sensor parameters and in-vivo parameters, then this information can be used by the calibration procedure. If in addition, b can be assumed to be 0, for example with a biointerface electrode configuration, then both m and b are known a priori, matched pairs are not needed for calibration, and the sensor can be completely benchtop calibrated.
Other methods for using information obtained prior to sensor insertion in sensor calibration are discussed in more detail elsewhere herein. In some embodiments, the long term sensor can be benchtop calibrated and then once implanted, the calibration of the data from the long term sensor can be adjusted using additional reference data, for example, reference data from a short term sensor. Typically for a long term sensor, as its biointerface matures, its m and b change.
This procedure would allow for accurate estimates of m, b, and time-lag assuming the time-lag of the short term sensor signal relative to blood glucose. Accordingly, reference data from a short term glucose sensor can be used in the initial calibration process described herein and shown in FIG. In the embodiment illustrated in FIG. Long term sensor A can be employed on the host 6 and calibrated using, e. Prior to the end of the lifespan of long term sensor A, long term sensor B can be implanted into the host 6.
Once long term sensor B is stable, sensor data from long term sensor A can be used to calibrate the sensor data from long term sensor B. This calibration process can be repeated for additional long term sensors employed on host 6 , so that a series of long term sensors can be employed, with the sensor data from each newly employed sensor being calibrated using sensor data from the previously employed long term sensor.
By this means, a patient can have continuity of data while only undergoing one procedure for each long term implant, for example, once per year.
In one example, Sensor A is implanted at time 0. After 11 months, Sensor B is implanted, and Sensor A is left in place. During the next month, Sensor B starts up and is calibrated using data from sensor A. At time 23 months, Sensor C is implanted and Sensor A is removed. Sensor B is used to calibrate Sensor C, and so forth for as long as the patient wishes to continue placing new sensors.
Other time frames of sensor implantation and overlap are also possible. It is known that some transdermal e. For example, when a first short term sensor's lifespan is nearing its end, a second short term sensor can be implanted into the user's tissue e.
In addition to providing data during the equilibration time of the second short term sensor thereby allowing data continuity , the first short term sensor can provide additional data, including calibration information, time lag information, drift information, and the like, to the second short term sensor to increase its intelligence and enhance its performance. In one situation, by providing at least two redundant sensors, transient problems experienced by one sensor can be negated by the use of the other sensor.
An analyte sensor uses any known method, including invasive, minimally invasive, and non-invasive sensing techniques, to provide an output signal indicative of the concentration of the analyte of interest. The output signal is typically a raw signal that is used to provide a value that can be used for calibrating another analyte sensor or an analyte sensor used in another application.
The analyte sensor s useful with the preferred embodiments can be any device capable of measuring the concentration of an analyte of interest. One exemplary embodiment is described below, which calibrates a long term implantable glucose sensor based on data from a short term implantable glucose sensor.
However, it can be understood that the devices and methods described herein can be applied to any device capable of detecting a concentration of analyte of and providing an output signal that represents the concentration of the analyte for use in calibrating another sensor.
In one embodiment, the short term sensors for use as described herein include a transcutaneous analyte sensor system that includes an applicator for inserting the transcutaneous transdermal analyte sensor under a host's skin. The sensor system includes a sensor for sensing the analyte, wherein the sensor is associated with a mounting unit adapted for mounting on the skin of the host. The mounting unit houses the electronics unit associated with the sensor and is adapted for fastening to the host's skin.
In the preferred embodiment of a system as depicted in FIG. The system can further include a receiver , such as is described in more detail with reference to FIG. The mounting unit housing 14 includes a base 24 adapted for mounting on the skin of a host, a sensor adapted for transdermal e. In one embodiment, an applicator 12 is provided for inserting the sensor 32 through the host's skin at the appropriate insertion angle with the aid of a needle see FIGS.
Preferably, the applicator comprises an applicator body 18 that guides the applicator components see FIGS. The mate between the applicator body base 60 and the mounting unit 14 can use any known mating configuration, for example, a snap-fit, a press-fit, an interference-fit, or the like, to discourage separation during use. One or more release latches 30 enable release of the applicator body base 60 , for example, when the applicator body base 60 is snap fit into the mounting unit For example, the electronics unit 16 can comprise a potentiostat, a power source for providing power to the sensor, other components useful for signal processing, and preferably an RF module for transmitting data from the electronics unit 16 to a receiver.
Electronics can be affixed to a printed circuit board PCB , or the like, and can take a variety of forms. Preferably, electronics unit 16 houses the sensor electronics, which comprise systems and methods for processing sensor analyte data. Examples of systems and methods for processing sensor analyte data are described in more detail in U. After insertion of the sensor using the applicator 12 , and subsequent release of the applicator 12 from the mounting unit 14 see FIGS.
The electronics unit 16 includes contacts on its backside not shown configured to electrically connect with the contacts 28 , such as are described in more detail with reference to FIGS. In preferred embodiments, the mounting unit 14 , also referred to as a housing, comprises a base 24 adapted for fastening to a host's skin.
The base can be formed from a variety of hard or soft materials, and preferably comprises a low profile for minimizing protrusion of the device from the host during use. In some embodiments, the base 24 is formed at least partially from a flexible material, which is believed to provide numerous advantages over conventional transcutaneous sensors, which, unfortunately, can suffer from motion-related artifacts associated with the host's movement when the host is using the device.
Flexibility or articulation is believed to increase adhesion with the use of an adhesive pad of the mounting unit 14 onto the skin, thereby decreasing motion-related artifact that can otherwise translate from the host's movements and reduced sensor performance.
In some embodiments, the contacts 28 are mounted on or in a subassembly hereinafter referred to as a contact subassembly 26 see FIG. In certain embodiments, the mounting unit 14 is provided with an adhesive pad 8 , preferably disposed on the mounting unit's back surface and preferably including a releasable backing layer 9. Thus, removing the backing layer 9 and pressing the base portion 24 of the mounting unit onto the host's skin adheres the mounting unit 14 to the host's skin.
Additionally or alternatively, an adhesive pad can be placed over some or all of the sensor system after sensor insertion is complete to ensure adhesion, and optionally to ensure an airtight seal or watertight seal around the wound exit-site or sensor insertion site not shown. In some embodiments, a double-sided adhesive pad is used to adhere the mounting unit to the host's skin. In other embodiments, the adhesive pad includes a foam layer, for example, a layer wherein the foam is disposed between the adhesive pad's side edges and acts as a shock absorber.
In some embodiments, the surface area of the adhesive pad 8 is greater than the surface area of the mounting unit's back surface. Alternatively, the adhesive pad can be sized with substantially the same surface area as the back surface of the base portion. Preferably, the adhesive pad has a surface area on the side to be mounted on the host's skin that is greater than about 1, 1. In some alternative embodiments, however, the adhesive pad can be smaller in surface area than the back surface assuming a sufficient adhesion can be accomplished.
In some embodiments, the adhesive pad 8 is substantially the same shape as the back surface 25 of the base 24 , although other shapes can also be advantageously employed, for example, butterfly-shaped, round, square, or rectangular. The adhesive pad backing can be designed for two-step release, for example, a primary release wherein only a portion of the adhesive pad is initially exposed to allow adjustable positioning of the device, and a secondary release wherein the remaining adhesive pad is later exposed to firmly and securely adhere the device to the host's skin once appropriately positioned.
The adhesive pad is preferably waterproof. Preferably, a stretch-release adhesive pad is provided on the back surface of the base portion to enable easy release from the host's skin at the end of the useable life of the sensor, as is described in more detail with reference to FIGS.
In some circumstances, it has been found that a conventional bond between the adhesive pad and the mounting unit may not be sufficient, for example, due to humidity that can cause release of the adhesive pad from the mounting unit. Accordingly, in some embodiments, the adhesive pad can be bonded using a bonding agent activated by or accelerated by an ultraviolet, acoustic, radio frequency, or humidity cure. In some embodiments, a eutectic bond of first and second composite materials can form a strong adhesion.
In some embodiments, the surface of the mounting unit can be pretreated utilizing ozone, plasma, chemicals, or the like, in order to enhance the bondability of the surface. A bioactive agent is preferably applied locally at the insertion site exit-site prior to or during sensor insertion.
Suitable bioactive agents include those which are known to discourage or prevent bacterial growth and infection, for example, anti-inflammatory agents, antimicrobials, antibiotics, or the like. It is believed that the diffusion or presence of a bioactive agent can aid in prevention or elimination of bacteria adjacent to the exit-site.
Additionally or alternatively, the bioactive agent can be integral with or coated on the adhesive pad, or no bioactive agent at all is employed. Preferably, a watertight waterproof or water-resistant sealing member 36 , also referred to as a sealing material or seal, fits within a contact holder 34 and provides a watertight seal configured to surround the electrical connection at the electrode terminals within the mounting unit in order to protect the electrodes and the respective operable connection with the contacts of the electronics unit 16 from damage due to moisture, humidity, dirt, and other external environmental factors.
In one embodiment, the sealing member 36 is formed from an elastomeric material, such as silicone; however, a variety of other elastomeric or sealing materials can also be used, for example, silicone-polyurethane hybrids, polyurethanes, and polysulfides.
Preferably, the sealing member is configured to compress within the contact subassembly when the electronics unit is mated to the mounting unit. In some embodiments, the sealing member 36 comprises a self-lubricating material, for example, self-lubricating silicone or other materials impregnated with or otherwise comprising a lubricant configured to be released during use.
In some embodiments, the sealing member 36 includes a self-sealing material, for example, one that leaches out a sealant such as a silicone oil. In some embodiments, bumps, ridges, or other raised portions not shown , can be added to a component of the sensor system, such as to the contact subassembly 26 e. Preferably, the sealing member is selected using a durometer.
A durometer is an instrument used for measuring the indentation hardness of rubber, plastics, and other materials. The hardness of plastics is most commonly measured by the Shore Durometer test or Rockwell hardness test. Both methods measure the resistance of plastics toward indentation and provide an empirical hardness value. The Shore A scale is used for softer rubbers while the Shore D scale is used for harder ones.
In preferred embodiments, the Shore A scale is employed in connection with selection of a sealing member. Because of the resilience of rubbers and plastics, the indentation reading may change over time, so the indentation time is sometimes reported along with the hardness number. The results obtained from this test are a useful measure of relative resistance to indentation of various grades of polymers.
Using a durometer in the selection of a sealing member enables selection of a material with optimal durometer hardness that balances the advantages of a lower durometer hardness with the advantages of a higher durometer hardness. In this clinical research, we aimed to identify factors that attribute to. Blood-alcohol proficiency test program. A preliminary survey has been performed to ascertain the validity of the blood alcohol analysis performed by a number of laboratories on a voluntary basis.
Values of accuracy and precision of the tests are presented. Lead levels - blood. This may include industrial workers and children Lead is common in the Monitoring Your Blood Sugar Level. Blood lead level is associated with non- alcoholic fatty liver disease in the Yangtze River Delta region of China in the context of rapid urbanization. China has undergone rapid urbanization in the past three decades. We enrolled subjects from 6 villages in the Yangtze River Delta Region.
Lead was measured by atomic absorption spectrometry. In total, Medians interquartile range of B-Pb were 5. Blood lead levels and chronic blood loss. This high affinity of lead for red cells may mean that chronic blood loss is a significant means for excretion of lead.
This study sought correlations between blood lead levels and clinical conditions involving chronic blood loss. During May, June and July, patients with normal hematocrits and red cell indices were identified from the hospital and clinic populations.
For each patient, age, race, sex and medical history were noted, and a whole blood sample was analyzed by flameless atomic absorption spectrophotometry. Age-and race-matched pairs showed a significant correlation of chronic blood loss with lead levels. Patients with the longest history of blood loss menstruating women had the lowest level mean 6. Post-menopausal women had levels 7.
The highest levels were among men who had no history of bleeding problems Chronic blood loss may be a major factor responsible for sexual differences in blood lead levels. Since tissue deposition of environmental pollutants is implicated in diseases, menstruation may represent a survival advantage for women.
Perinatal alcohol exposure enhances nocistatin levels in adulthood. In earlier experiments perinatal hormonal imprinting by alcohol decreased the hormone content of immune cells for life. Our data suggest that alcohol consumption during lactation can cause a life-long influence on nocistatin levels in the offspring and most likely modify nocistatin-related functions such as pain tolerance.
Cognitive dysfunction, MRI findings and manganese levels in alcoholics. Alcoholic patients have been known to have brain atrophy and cognitive dysfunction. However, recent studies have reported bilateral signal hyperintensities of the globus pallidus on T1-weighted magnetic resonance imaging MRI in liver failure, findings that are typically associated with manganese intoxication.
In addition, a significant correlation was seen between pallidal signal intensity P. However, no significant correlations were found between pallidal signal intensity ratio and any of the WAIS-R parameters. These findings suggest that no direct connection exists between cognitive dysfunction and pallidal hyperintensity in alcoholic patients with liver cirrhosis.
We confirmed that brain MRI in alcoholics could detect pallidal signal hyperintensity, suggesting severe liver dysfunction. In addition to diagnosis, brain MRI is useful for therapeutic psychoeducation to alcoholic patients with liver cirrhosis, visualizing the severe liver dysfunction. Comparison of spectroscopically measured tissue alcohol concentration to blood and breath alcohol measurements. Alcohol testing is an expanding area of interest due to the impacts of alcohol abuse that extend well beyond drunk driving.
However, existing approaches such as blood and urine assays are hampered in some testing environments by biohazard risks. A noninvasive, in vivo spectroscopic technique offers a promising alternative, as no body fluids are required. The purpose of this work is to report the results of a subject clinical study designed to characterize tissue alcohol measured using near-infrared spectroscopy relative to venous blood , capillary blood , and breath alcohol.
Comparison of blood and breath alcohol concentrations demonstrated significant differences in alcohol concentration [root mean square of 9. A first-order kinetic model was used to estimate the contribution of alcohol pharmacokinetics to the differences in concentration observed between the blood , breath, and tissue assays. All pair-wise combinations of alcohol assays were investigated, and the fraction of the alcohol concentration variance explained by pharmacokinetics ranged from Accounting for pharmacokinetic concentration differences, the accuracy and precision of the spectroscopic tissue assay were found to be comparable to those of the blood and breath assays.
Examination of liver and muscle glycogen and blood glucose levels The need for blood alcohol concentration BAC legislation in Nigeria. The pharmacology, clinical and sports implications of indulgence in alcohol and the debate on its legal status are highlighted in this article.
The information presented could offer both clinical and safety benefits to psychomotor tasks executors and road safety professionals. Blood alcohol concentration BAC , Effect of flomoxef on blood coagulation and alcohol metabolism. A disulfiram-like effect caused by inhibition of aldehyde dehydrogenase was observed for NMTT-containing antibiotics.
Studies were carried out on healthy volunteers and on rats. Eight-day treatment with 2 g flomoxef i. This defect was quickly normalized by vitamin K injection. There were no differences between oxacephem 1-O and cephem 1-S compounds with respect to effects on blood clotting and platelet aggregation. Flomoxef and its side chain HTT showed no influence on alcohol metbolism. Consumption of alcohol and blood pressure: Prevention and reduction of excessive use of alcohol represents damages to society in general.
In turn, arterial hypertension is the main attributable risk factor premature life lost years and disability. A baseline data of total of 7, participants volunteers between 35 and 74 years of age, of both genders, in six educational and research institutions of three different regions of the country were interviewed between Socioeconomic, haemodynamic, anthropometric and health data were collected in the research centers of ELSA-Brasil.
Alcohol consumption was estimated and categorized regarding consumption and pattern of ingestion. The consumption of alcohol beverages increases the odds of elevated blood pressure, especially among excessive drinkers. Therefore alcohol consumption needs a more robust regulation in view of its impact on population.
Estimating the measurement uncertainty in forensic blood alcohol analysis. For many reasons, forensic toxicologists are being asked to determine and report their measurement uncertainty in blood alcohol analysis. While understood conceptually, the elements and computations involved in determining measurement uncertainty are generally foreign to most forensic toxicologists. Several established and well-documented methods are available to determine and report the uncertainty in blood alcohol measurement.
A straightforward bottom-up approach is presented that includes: A hypothetical example is presented that employs reasonable estimates for forensic blood alcohol analysis assuming headspace gas chromatography. These computations are easily employed in spreadsheet programs as well. Determining and reporting measurement uncertainty is an important element in establishing fitness-for-purpose. Indeed, the demand for such computations and information from the forensic toxicologist will continue to increase.
Effects of different blood alcohol concentrations and post- alcohol impairment on driving behavior and task performance. A study using simulator methodology was conducted to investigate the effects of 1 different blood alcohol concentrations BAC of 0, 0. Two driving sessions were investigated, that is, drunk driving and post- alcohol driving, with each requiring approximately 20 min of driving. Eight licensed drivers 6 males, 2 females participated in this 2 road complexities x 2 simulated driving sessions x 4 levels of BAC within-subjects experiment.
The study revealed that higher BAC levels were associated with lower performing driving behavior. The driver's mental workload reached the highest values in the post- alcohol session. In terms of tasks involving divided attention, the traffic sign distance estimation showed significant deterioration with increased BAC levels. The relationship between drunk-driving behavior and alcohol dosage was supported in this study. Noticeably, no significant difference was found between drunk driving and post- alcohol driving, indicating that even in the post- alcohol situation, the impairment still remained significant enough to jeopardize traffic safety as much as it does in the case of drunk driving.
In real-life situations, adopting a rest-time strategy to avoid post- alcohol impairment effects may not be the most appropriate solution by drivers; rather, drivers should be given some tests to verify the probability of post- alcohol effects on driving. Why control blood glucose levels? The controversy as to the relationship between the degree of control of diabetes and the progression of the complications of the disease has not been solved. However, in this review, various studies suggesting a relationship between the metabolic abnormality and the diabetic complications are examined.
The disadvantages of the uncontrolled diabetes mellitus can be divided into two major categories-short-term and long-term. The short-term disadvantages of controlled diabetes mellitus include the following: The long-term disadvantages of uncontrolled diabetes melitus include the following: It is suggested that until the question of control can absolutely be resolved, the recommendation is that the blood glucose levels should be controlled as close to the normal as possible.
Genetic variation and epigenetic modification of the prodynorphin gene in peripheral blood cells in alcoholism. Dynorphins are critically involved in the development, maintenance and relapse of alcoholism. Alcohol -induced changes in the prodynorphin gene expression may be influenced by both gene polymorphisms and epigenetic modifications.
The present study of human alcoholics aims to evaluate DNA methylation patterns in the prodynorphin gene PDYN promoter and to identify single nucleotide polymorphisms SNPs associated with alcohol dependence and with altered DNA methylation. In alcoholics , DNA methylation increased in three of the seven CpG sites investigated, as well as in the average of the seven CpG sites. Data stratification showed lower increase in DNA methylation levels in individuals reporting craving and with higher levels of alcohol consumption.
Association with alcoholism was observed for rs and the presence of the minor allele G was associated with reduced DNA methylation at PDYN promoter in females and younger subjects.
Genetic and epigenetic factors within PDYN are related to risk for alcoholism , providing further evidence of its involvement on ethanol effects. These results might be of relevance for developing new biomarkers to predict disease trajectories and therapeutic outcome. Serum alcohol levels correlate with injury severity and resource Alcohol consumption leads to violence and poor judgement. The resultant trauma is the leading cause of emergency department visits. The purpose of this prospective study was to establish the prevalence of positive blood alcohol and The purpose of this study was to explore the peptides that are related to acute reduction of blood pressure after alcohol drinking.
Alcohol caused significant decreases in systolic and diastolic blood pressure levels at 45 min. A proposal of updating the blood and urine sampling protocol]. The present paper emphasizes the most common mistakes committed at the beginning of an analytical procedure. To shorten the time and decrease the cost of determinations of substances with similar to alcohol activity, it is postulated to introduce mass-scale screening analysis of saliva collected from a living subject at the site of the event, with all positive results confirmed in blood or urine samples.
If no saliva sample is collected for toxicology, a urine sample, allowing for a stat fast screening analysis, and a blood sample, to confirm the result, should be ensured. Inappropriate storage of a blood sample in the tube without a preservative can cause sample spilling and its irretrievable loss.
The effect of alcoholism on secretor status of blood groups A and B One hundred and fifty were alcoholics and one hundred and fifty non- alcoholics served as controls. In the alcoholic group, seventy five were blood group B while seventy five were blood group A.
Fourty two out of the Blood Glucose Levels and Problem Behavior. The relationship between varying blood glucose levels and problem behavior during daily scheduled activities was examined.
The effects that varying blood glucose levels had on problem behavior during daily scheduled activities were examined. Prior research has shown that differing blood glucose levels can affect behavior and mood. Blood lipid levels in a rural male population. Farmers have a low risk for cardiovascular disease, which may be related to a favourable blood lipid profile. In order to study the blood lipid levels and evaluate the effect of other cardiovascular risk factors on the blood lipid profile, this cross-sectional study was made.
A total of farmers and non-farming rural men in nine different Swedish counties were examined, interviewed, and replied to questionnaires. The inter-relationships between different risk factors were analysed using a multivariate linear regression model. The farmers had a significantly more favourable blood lipid profile than the non-farmers although the total cholesterol levels were almost the same for the two groups.
In the total study population there were significant positive relationships between total cholesterol level and body mass index BMI , diastolic blood pressure and smoking. Differences between farmers and other rural males were seen, especially with respect to the effect of physical activity and psychosocial factors.
Student drinking patterns and blood alcohol concentration on commercially organised pub crawls in the UK. Commercial student pub crawls are associated with high levels of alcohol consumption, and are of growing concern amongst public health and student bodies. However, little is currently known about drinking behaviours whilst participating in these events. A questionnaire was implemented amongst students attending commercial pub crawls across three UK events. Questions established alcohol consumption patterns up to the point of interview and throughout the remaining night out, and pub crawl experience.
Breathalyser tests were used to measure breath alcohol concentration converted to blood alcohol concentration [BAC] at interview. Drinkers reported consuming a median of Median BAC of drinkers at the time of interview was 0. Organisers, local authorities, universities and students should all be involved in ensuring the effective management of pub crawls, including implementation of harm prevention measures. Blood creatinine level in postmortem cases. Blood chemical analysis for the diagnosis of diseases in forensic cases should be conducted in the same way as for clinical cases.
However, it is sometimes difficult to obtain serum samples in forensic cases because of postmortem changes such as hemolysis and putrefaction. This study aimed to evaluate renal function in postmortem cases by blood creatinine analysis. The blood creatinine level was measured by high performance liquid chromatography HPLC using whole blood samples taken from 77 postmortem cases, and the relationships between blood creatinine level , postmortem interval, and cause of death were examined.
The median blood creatinine level was found to be 1. The blood creatinine level was stable for 3 days after death and gradually increased after that period, in line with a previous study using enzymatic analysis that found the serum creatinine level was stable in the early postmortem period.
The blood creatinine level was high in the cases of blunt injury, intoxication, and in deaths caused by fire. This was considered to reflect acute renal dysfunction. However, the postmortem blood creatinine level remained higher than the clinical normal value despite omitting cases with renal dysfunction from the analysis.
Therefore, we next investigated the change in postmortem creatinine levels in mice and found that the blood creatinine level increased with the emergence of rigor mortis.
Our findings indicate that HPLC is useful in the postmortem evaluation of renal function even in the cases where serum cannot be obtained. However, the presence of rigor mortis should be considered in the evaluation of blood creatinine values. Published by Elsevier Ireland Ltd.
Wondering if adding a glass of wine or beer might help lower your blood glucose if it is high? The effects of alcohol can be unpredictable and it is not recommended as a treatment for high blood glucose.
The risks likely outweigh any benefit that may be seen in blood glucose alone. Alarming levels of carboxyhemoglobin in banked blood. To determine the level of carboxyhemoglobin found in banked blood in the Albany, NY region. The blood bank of a university tertiary care hospital in Albany, NY. The average COHb level was 0. Certain high-risk populations eg, cyanotic neonates undergoing cardiopulmonary bypass may be especially at risk.
Joint effect of alcohol consumption and educational level on alcohol -related medical events. Information on highest attained education 1 year before study entry and hospital and mortality data on alcohol -related medical events were obtained through linkage to nationwide registries. We performed analyses using the Aalen We investigated the joint effect of alcohol consumption and educational level on the rate of alcohol -related medical events.
We pooled seven prospective cohorts from Denmark that enrolled 74, men and women age 30—70 years study period, to During follow-up 1,, person-years , a total of alcohol -related events occurred. Adolescent alcohol use reflects community- level alcohol consumption irrespective of parental drinking. Risk factors for adolescent alcohol use are typically conceptualized at the individual level , and school- and community- level risk factors have received little attention.
Based on the theoretical understanding of youth alcohol consumption as a reflection of community social practice, we analyzed Furthermore, we investigated whether the association between community- level AAC and adolescent drunkenness was attenuated after Diabetes Hypoglycemia Diabetes Control: Cerebral blood flow and cerebrovascular response to acetazolamide in patients with chronic alcoholism.
Cerebral blood flow and cerebrovascular response to acetazolamide were studied in 12 patients with chronic alcoholism and 12 age matched healthy controls. Blood flows in the cerebral cortex, thalamus, and putamen were significantly lower in the chronic alcoholic group than in the healthy control group.
The increase in blood flow caused by acetazolamide did not show any significant difference between the two groups. These findings suggest that the decreased cerebral blood flow i The association of alcohol intake with gamma-glutamyl transferase GGT levels: Evidence for correlated genetic effects. Blood levels of gamma-glutamyl transferase GGT are used as a marker for heavy alcohol use. The role of GGT in the anti-oxidant defense mechanism that is part of normal metabolism supposes a causal effect of alcohol intake on GGT.
However, there is variability in the response of GGT. Skin preparation with alcohol versus alcohol followed by any antiseptic for preventing bacteraemia or contamination of blood for transfusion. Blood for transfusion may become contaminated at any point between collection and transfusion and may result in bacteraemia the presence of bacteria in the blood , severe illness or even death for the blood recipient.
Donor arm skin is one potential source of blood contamination, so it is usual to cleanse the skin with an antiseptic before blood donation. One-step and two-step alcohol based antiseptic regimens are both commonly advocated but there is uncertainty as to which is most effective. To assess the effects of cleansing the skin of blood donors with alcohol in a one-step compared with alcohol in a two-step procedure to prevent contamination of collected blood or bacteraemia in the recipient.
All randomised trials RCTs comparing alcohol based donor skin cleansing in a one-step versus a two-step process that includes alcohol and any other antiseptic for pre-venepuncture skin cleansing were considered. Quasi randomised trials were to have been considered in the absence of RCTs. Two review authors independently assessed studies for inclusion.
We did not identify any eligible studies for inclusion in this review. It is therefore unclear whether a two-step, alcohol followed by antiseptic skin cleansing process prior to blood donation confers any reduction in the risk of blood contamination or bacteraemia in blood recipients, or conversely whether a one-step process increases risk above that associated with a two-step process. Determination of indigenous and foreign alcoholic beverages' levels The comparative levels of indigenous and foreign alcoholic beverages in the urine of 24 University students after drinking a cup or shot of the beverages have been reported.
The Fourier Transform infrared spectroscopy was used for the analysis. A comparative study of blood alcohol concentrations in Australian night-time entertainment districts. There is little research describing how intoxication levels change throughout the night in entertainment districts. This research aims to describe levels of alcohol intoxication across multiple Australian metropolitan and regional nightlife districts. This study was conducted in the night-time entertainment districts of three metropolitan cities Sydney, Melbourne and Perth and two regional cities Wollongong and Geelong in Australia.
Of the individuals approached to participate in the study, [ There was a linear increase in blood alcohol concentration BAC levels throughout the night. Post hoc testing revealed significantly more highly intoxicated participants i. There was no age differences in intoxication earlier in the night, but after midnight, patrons over the age of 21 showed increasing BAC levels. There is a consistent trend across the cities of high to very high levels of intoxication later in the night, with trends after midnight being significantly different to those before.
Full Text Available BackgroundFew studies have examined the association between mercury exposure and obesity. The aim of this study is to investigate the association between blood mercury concentrations and indices of obesity in adults. MethodsA total of healthy subjects, aged 30 to 64 years, who had no history of cardiovascular or malignant disease, were examined. Anthropometric and various biochemical profiles were measured.
ResultsAll subjects were divided into three groups according to blood mercury concentrations. Compared with the subjects in the lowest tertile of mercury, those in the highest tertile were more likely to be male; were current alcohol drinkers and smokers; had a higher body mass index BMI, waist circumference WC, and VAT; had higher levels of blood pressure, fasting glucose, and insulin resistance; and consumed more fish. Further studies are warranted to confirm our findings.
Alcohol consumption and its impact on the risk of high blood pressure in Russia. This study aims to examine the causal effect of alcohol consumption on the risk of high blood pressure in Russia.
Using data from the Russian Longitudinal Monitoring Survey, we estimated the influence of alcohol consumption on high blood pressure, controlling for social and other factors related to alcohol use. To address the issue of causality, we instrumented alcohol consumption by the number of frequent alcohol drinkers in the household. We found that frequent consumption of vodka and beer has an adverse impact on health.
In particular, frequent vodka consumption increases the likelihood of high blood pressure by 2. Controlling for the endogeneity of frequent alcohol consumption using the instrumental variable method produces an even larger effect for frequent vodka consumption, with a marginal effect of 7. Prevention policies as well as government programs aimed at treating alcohol -related health outcomes should take into consideration the significant adverse effect of alcohol consumption on high blood pressure.
It is also recommended that policy interventions aimed to address alcohol addiction issues in Russia explicitly differentiate between vodka and beer drinkers. Full Text Available According to WHO, the world takes place every year approximately suicides and suicide attempts of 7 million. Since , Russia ranks 2nd in the world after Lithuania, in the level of suicides, and is among the countries with the linear dependence of frequency of suicides on the level of alcohol consumption.
Install a quantitative connection between the frequency of suicide with alcohol consumption and mortality from alcoholism in the world. For data analysis we used correlation and regression methods. We found significant positive correlation of mortality coefficient MK from suicide for men and women with consumption of alcoholic beverages spirits, wine and beer and mortality from alcoholism.
The gender differences are revealed. A complete rejection of the consumption of alcohol reduces the MK from suicide of men in the world at According to the regression analysis the average daily level of consumption of strong alcohol in the world is The increase in the consumption of strong alcohol to 3 g per day 1 kg per year increases the MK from suicide in men up to The increase in the MK of alcoholism of men.
The authors of the paper give a brief historical overview of the development of experimental alcohology in the former Czechoslovakia. Enhanced attention is paid to tests of work quality control of toxicological laboratories. Information on results of control tests of blood samples using the method of gas chromatography in Slovakia and within a world-wide study "Eurotox " is presented.
There are pointed out the pitfalls related to objective evaluation of the analysis results interpreting alcohol concentration in biological materials and the associated need to eliminate a negative influence of the human factor.
The authors recommend performing analyses of alcohol in biological materials only at accredited workplaces and in the case of samples storage to secure a mandatory inhibition of phosphorylation process. There are analysed the reasons of numerical differences of analyses while taking evidence of alcohol in blood and in exhaled air. The authors confirm analysis accuracy using the method of gas chromatography along with breath analysers of exhaled air.
They highlight the need for making the analysis results more objective also through confrontation with the results of clinical examination and with examined circumstances. The authors suggest a method of elimination of the human factor, the most frequently responsible for inaccuracy, to a tolerable level safety factor and the need of sample analysis by two methods independent of each other or the need of analysis of two biological materials. These experimental findings suggest that maternal alcohol consumption may facilitate HIV infection, promoting vertical transmission of HIV.
The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats. In the present study, we examined whether Acer okamotoanum A. Pre-treatment with the sap significantly decreased the blood ethanol and acetaldehyde concentrations after 5 h when compared with ethanol treatment alone a negative control.
The data suggest that sap pre-treatment enhanced the alcohol metabolism rate in the rat liver. To investigate the involvement of mitochondrial regulation in the ethanol-induced hepatocyte apoptosis, we carried out an immunohistochemical analysis of Bax and Bcl Pre-treatment with sap significantly decreased Bax expression and increased Bcl-2 expression 7 h after ethanol administration when compared with the negative control. The data suggest that A.
Personality and alcohol metacognitions as predictors of weekly levels of alcohol use in binge drinking university students. This study investigated the relative contribution of the Big 5 personality factors and alcohol metacognitions in predicting weekly levels of alcohol use in binge drinking university students.
No research to date has investigated whether either of these constructs predicts levels of weekly alcohol use in binge drinkers. Pearson product-moment correlations showed that weekly levels of alcohol use were negatively correlated with agreeableness and conscientiousness and positively correlated with positive alcohol metacognitions about cognitive self-regulation, negative alcohol metacognitions about uncontrollability and negative alcohol metacognitions about cognitive harm.
A hierarchical regression analysis revealed that conscientiousness and positive alcohol metacognitions about cognitive self-regulation were the only two significant predictors of weekly levels of alcohol use when controlling for gender.
These findings show that being male, low on conscientiousness and high on positive alcohol metacognitions about cognitive self-regulation raises the risk for increased weekly levels of alcohol use in binge drinking university students.
The implications of these findings are discussed. Work related stress and blood glucose levels. The aim of the study is to evaluate work-related subjective stress in a group of workers on a major Italian company in the field of healthcare through the administration of a valid "questionnaire-tool indicator" HSE Indicator Tool , and to analyze any correlation between stress levels taken from questionnaire scores and blood glucose values.
We studied a final sample consisting of subjects with different tasks. The HSE questionnaire - made up of 35 items divided into 7 organizational dimensions with 5 possible answers - has been distributed to all the subjects in occasion of the health surveillance examinations provided by law. The questionnaire was then analyzed using its specific software to process the results related to the 7 dimensions.
These results were compared using the Pearson correlation and multiple linear regression with the blood glucose values obtained from each subject. From the analysis of the data the following areas resulted critical, in other words linked to an intermediate yellow area or high red area condition of stress: A significant positive correlation p work stress can be statistically associated with increased levels of blood glucose.
Correlation between plasma homocysteine levels and craving in alcohol dependent stabilized patients. Homocysteine is a sulfur amino acid strictly related with alcohol consumption. In alcoholics , hyperhomocysteinemia can increase the risk of various alcohol -related disorders such as: To evaluate the correlation among serum homocysteine concentrations, craving, hazardous and harmful patterns of alcohol consumption in patients stabilized for withdrawal symptoms.
Participants were adult outpatients accessed at the Addiction Treatment Unit. Alcoholism was assessed using the following tools: Furthermore, during the first visit a blood sample was taken from all patients to measure the plasma concentration of both homocysteine and Carboxy Deficient Transferrin CDT.
Differences between groups in socio-demographic and clinical characteristics were analyzed using the t-test and the Mann-Whitney's U test for normally and non-normally distributed data, respectively. Correlation between clinical scale scores and plasma concentration of homocysteine and CDT was evaluated using the Pearson's correlation coefficient and the Kendall's Tau-b bivariate correlation coefficient for normally and non-normally distributed data, respectively.
Our study included 92 patients. No difference was found in socio-demographic characteristics between groups. Production of inflammatory cytokines by peripheral blood monocytes in chronic alcoholism: Controversial results have been reported about the effects of alcoholism on the functionality of monocytes.
In the present study we analyze the effects of chronic alcoholism on the intracellular production of inflammatory cytokines by peripheral blood PB monocytes. Conversely, circulating monocytes form ALCET patients showed an abnormally low spontaneous and stimulated production of inflammatory cytokines. Money and freedom is the greatest way to change, may you be rich and continue to help other people.
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