Biomedical subjects

S R Myers

Publications and source records attributed to S R Myers.

At least 19 recordsLinked to original sources

PubMed2005

Case-controlled study of patients with self-inflicted burns.

The main objectives of this study were to investigate whether patients with self-inflicted burns have larger burns, and a worse outcome, than patients with accidental burns. The secondary objective was to examine patient pre-injury characteristics to identify ways of preventing the burn occurring. A case-controlled study was performed: 36 deliberate self-burn patients were matched separately to two groups of accidental burn patients. The first group was used to compare burn severity. Patients were matched for age and sex; they were excluded if they had a psychiatric diagnosis, or a non-burn injury. The second group was used to compare outcome. The same matching and exclusion criteria were used as in the first group, with the addition of burn-size. Deliberate self-burn patients have significantly larger burns (p<0.01; median total body surface area (TBSA) 10% versus 1.5%) than accidental burn patients. They also stay in hospital longer, even when matched for burn-size (p<0.02; median stay 15 days versus 9 days). Self-inflicted burns occurred in supervised environments in 28% of cases. The number of deliberate self-burns could be reduced with simple interventions such as restricting smoking in hospitals and prisons, and also by identifying high-risk patients. The poor outcome from deliberate self-burns could be improved by well-coordinated multidisciplinary patient management with early psychiatric team involvement.

Accidents↗

PubMed2004

Don't miss HIT (heparin induced thrombocytopenia).

Thrombocytopenia following a burn injury can cause serious complications. There are several possible causes including the burn itself, drugs, sepsis and disseminated intravascular coagulation (DIC). A case report of a patient who developed heparin induced thrombocytopenia (HIT) whilst on haemofiltration for acute renal failure is presented. The aetiology of thrombocytopenia in a burns patient and its management is discussed. The key to effective treatment of thrombocytopenia is identification of the cause. HIT is an important diagnosis to include in the differential.

Acute Kidney Injury↗

PubMed2003

A reappraisal of the role of cerium in burn wound management.

A rare earth element, cerium, was introduced as an antibacterial agent in 1976 but has rarely been used due to the emphasis on wound excision. Used in combination with silver sulphadiazine, it may improve patient survival when excision is not possible.

Administration, Topical↗

PubMed2001

Modulation of biomarkers by chemopreventive agents in smoke-exposed rats.

Chemoprevention opens new perspectives in the prevention of cancer and other chronic degenerative diseases associated with tobacco smoking, exploitable in current smokers and, even more, in exsmokers and passive smokers. Evaluation of biomarkers in animal models is an essential step for the preclinical assessment of efficacy and safety of potential chemopreventive agents. Groups of Sprague Dawley rats were exposed whole body to a mixture of mainstream and sidestream cigarette smoke for 28 consecutive days. Five chemopreventive agents were given either with drinking water (N-acetyl-L-cysteine, 1 g/kg body weight/day) or with the diet (1,2-dithiole-3-thione, 400 mg; Oltipraz, 400 mg; phenethyl isothiocyanate, 500 mg; and 5,6-benzoflavone, 500 mg/kg diet). The monitored biomarkers included: DNA adducts in bronchoalveolar lavage cells, tracheal epithelium, lung and heart; oxidative damage to pulmonary DNA; hemoglobin adducts of 4-aminobiphenyl and benzo(a)pyrene-7,8-diol-9,10-epoxide; micronucleated and polynucleated alveolar macrophages and micronucleated polychromatic erythrocytes in bone marrow. Exposure of rats to smoke resulted in dramatic alterations of all investigated parameters. N-Acetyl-L-cysteine, phenylethyl isothiocyanate, and 5,6-benzoflavone exerted a significant protective effect on all alterations. 1,2-Dithiole-3-thione was a less effective inhibitor and exhibited both a systemic toxicity and genotoxicity in alveolar macrophages, whereas its substituted analogue Oltipraz showed limited protective effects in this model. Interestingly, combination of N-acetyl-L-cysteine with Oltipraz was the most potent treatment, resulting in an additive or more than additive inhibition of smoke-related DNA adducts in the lung and hemoglobin adducts. These results provide evidence for the differential ability of test agents to modulate smoke-related biomarkers in the respiratory tract and other body compartments and highlight the potential advantages in combining chemopreventive agents working with distinctive mechanisms.

Acetylcysteine↗

PubMed1999

How far can a juxtacrine signal travel?

Juxtacrine signalling is the process of cell communication in which ligand and receptors are both anchored in the cell membrane. We develop three mathematical models for this process, involving different mathematical representations of the dynamics of membrane-bound ligand and free and bound receptors, within an epithelial sheet. We consider the dynamics of this system following a localized disturbance, such as would be provided by a source of ligand or by the generation of a free edge via wounding. We study the ability of the juxtacrine mechanism to transmit a signal away from this disturbance, and show analytically that the spatial half-life of the signal can in fact be arbitrarily large. This result is quite general, since we use a generic reaction kinetic scheme; the key assumption is that ligand and receptor production are both upregulated by binding. Moreover, the result applies to all three of our model formulations. We conclude by discussing applications of the result to the particular case of the transforming growth factor alpha binding to epidermal growth factor receptor in epidermal wound healing.

Animals↗

PubMed1999

Anterior femoroacetabular impingement after periacetabular osteotomy.

As experience with the Bernese periacetabular osteotomy has grown, an unexpected observation in a group of patients has alerted the authors to the risk of a secondary impingement syndrome that may occur some time after the periacetabular osteotomy. This possibly may explain residual pain and limited range of motion in a larger group of patients. The impingement is produced by abutment of the femoral head or head to neck junction on the anterior rim of the properly aligned acetabulum. The symptoms are those of restricted flexion, and limited or absent internal rotation in flexion, with variable groin pain. Magnetic resonance imaging studies may reveal acetabular labral disease and adjacent cartilage damage associated with the impingement. Lack of anterior or anterolateral offset between the femoral neck and head results in neck to rim contact when the hip is flexed and/or internally rotated. Before the periacetabular osteotomy this is compensated by the lack of anterior acetabular coverage, but after proper correction the mismatch becomes apparent. The authors recently have devised a routine during the periacetabular osteotomy procedure whereby after the acetabular fragment is corrected into the desired position, the joint is opened, visually inspected, and palpated for impingement with the hip flexed and internally rotated. When necessary, a resection osteoplasty of the femoral neck to head junction is performed to improve the head and neck offset and reduce the anterior contact. This, in the short term, has provided satisfactory prevention of postoperative impingement.

Acetabulum↗

PubMed1998

Analysis of minocycline by high-performance liquid chromatography in tissue and serum.

A sensitive and rapid reversed-phase high-performance liquid chromatography assay can be used to accurately determine serum and tissue minocycline concentrations. Minocycline is a broad spectrum tetracycline derivative with many applications. Tissue and serum samples were obtained from guinea pigs that had received either topical or intravenous minocycline. Samples were extracted using a Sep-Pak C18 cartridge and were injected into a microBondapak C18 column with an isocratic methanol mobile phase. Samples were analyzed using UV detection and produced sharp peaks with a retention time of 2.5 min. The lower limit of detection was 100 ng and drug recovery was 61%. This method greatly facilitated the analysis of minocycline while allowing for sensitivity.

Administration, Topical↗

PubMed1998

Effects of non-covalent self-association on the subcutaneous absorption of a therapeutic peptide.

PURPOSE: To utilize an acylated peptide as a model system to investigate the relationships among solution peptide conformation, non-covalent self-association, subcutaneous absorption and bioavailability under pharmaceutically relevant solution formulation conditions. METHODS: CD spectroscopy, FTIR spectroscopy, equilibrium sedimentation, dynamic light scattering, and size exclusion chromatography were employed to characterize the effects of octanoylation on conformation and self-association of the 31 amino acid peptide derivative des-amino-histidine(7) arginine(26) human glucagon-like peptide (7-37)-OH (IP(7)R(26)GLP-1). Hyperglycemic clamp studies were performed to compare the bioavailability, pharmacokinetics, and pharmacodynamics of solution formulations of oct-IP(7)R(26)GLP-1 administered subcutaneously to normal dogs. RESULTS: Octanoylation of IP(7)R(26)GLP-1 was shown to confer the propensity for a major solvent-induced conformational transition with an accompanying solvent- and temperature-dependent self-association behavior. Formulations were characterized that give rise to remarkably different pharmacodynamics and pharmacokinetics that correlate with distinct peptide conformational and self-association states. These states correspond to: (i) a minimally associated alpha-helical form (apparent molecular weight = 14 kDa), (ii) a highly associated, predominantly beta-sheet form (effective molecular diameter 20 nm), and (iii) an unusually large, micelle-like soluble beta-sheet aggregate (effective molecular diameter 50 nm). CONCLUSIONS: Bioavailability and pharmacokinetics of a self-associating peptide can be influenced by aggregate size and the ease of disruption of the non-covalent intermolecular interactions at the subcutaneous site. Hydrophobic aggregation mediated by seemingly innocuous solution formulation conditions can have a dramatic effect on the subcutaneous bioavailability and pharmacokinetics of a therapeutic peptide and in the extreme, can totally preclude its absorption. A size exclusion chromatographic method is identified that distinguishes subcutaneously bioavailable aggregated oct-IP(7)R(26)GLP-1 from non-bioavailable aggregated oct-IP(7)R(26)GLP-1.

Amino Acid Sequence↗

PubMed1998

Metabolism of 3-butene-1,2-diol in B6C3F1 mice. Evidence for involvement of alcohol dehydrogenase and cytochrome p450.

3-Butene-1,2-diol (BDD), a metabolite of 1,3-butadiene, is rapidly metabolized by B6C3F1 mice at doses ranging from 10 to 250 mg/kg. Calculation of plasma clearance suggested that the kinetics of BDD metabolism were dose-dependent. Clearance varied 5-fold in this dose range. Urinary excretion of BDD was also dose-dependent but did not exceed 5% of the administered dose. A small fraction of the dose (<1%) was excreted as glucuronide or sulfate conjugates. Benzylimidazole, a cytochrome P450 inhibitor, decreased the clearance of BDD (25 mg/kg) by 44%, whereas 4-methylpyrazole, an alcohol dehydrogenase and cytochrome P450 inhibitor, decreased BDD clearance by 82%. BDD administration (250 mg/kg) resulted in depletion of hepatic and renal nonprotein thiols, by 48 and 22%, respectively. Pretreatment of mice with 4-methylpyrazole provided partial protection against depletion of nonprotein thiols, whereas pretreatment with benzylimidazole was ineffective. Incubation of BDD with NADPH and mouse liver microsomes resulted in time-dependent inactivation of p-nitrophenol hydroxylase (PNPH) activity, a marker for cytochrome P450. Inclusion of glutathione, with or without glutathione peroxidase, did not attenuate the inactivation of PNPH, whereas deferoxamine, superoxide dismutase, catalase, and mannitol provided modest protection. These results are consistent with suicide inhibition of PNPH by BDD, with a minor role for reactive oxygen species in the loss of PNPH. Treatment of mice with BDD (250 mg/kg) inactivated hepatic microsomal PNPH activity by 50% after 60 min. These results suggest that BDD is extensively and rapidly metabolized in mice, and they provide evidence for the formation of reactive intermediates that could play a role in the toxicity of 1, 3-butadiene.

Alcohol Dehydrogenase↗

PubMed1997

The use of a urine mutagenicity assay in the monitoring of environmental exposure to genotoxins.

Urinary bacterial mutagenicity was used as a biomarker of exposure to ambient air pollution in a group of women working outdoors in the city of Teplice (TP; Northern Bohemia) with higher levels of air pollution than a similar group of women in the city of Prachatice (PT; Southern Bohemia). The Salmonella typhimurium plate incorporation assay with the TA98 and YG1041 strains and microsuspension assay with the YG1041 strain were used for testing the urinary mutagenicity. PAH and their metabolites were analyzed by HPLC and GC/MS methods. The significantly higher values of most PAHs/metabolites detected in a TP group confirmed the differences of PAH exposures between both groups. In the plate incorporation assay, the TA98 strain was not able to detect the increase in urinary mutagenicity, but, for the YG1041 strain, the urinary mutagenicity was clearly determined with a significant difference in number of YG1041 + S9 revertants between the TP and PT groups. The microsuspension assay increased the mean response by about 10-fold over the standard plate test; however, no statistical difference between TP and PT groups was found due to high interindividual variability and small sample size. Comparing the urinary PAH/metabolites to urinary mutagenicity, significant correlations were observed between the plate incorporation mutagenicity results with the YG1041 revertants in the presence of metabolic activation and several of the urinary PAH/metabolites. On the contrary, in the microsuspension assay, several urinary PAH/metabolites correlated significantly with the YG1041 revertants only in the absence of metabolic activation. This may indicate the influence of different treatment conditions of assays on the urinary mutagenicity results. The results suggest the insufficient sensitivity of the TA98 tester strain to determinate low urinary level of mutagens. On the contrary, the use of the YG1041 tester strain increases the probability of detecting an effect of environmental exposure and seems to be applicable to biological monitoring. To definitely replace the standard plate incorporation assay with the microsuspension method is not possible without further comparative studies.

Adult↗

PubMed1997

Suppository administration of chemotherapeutic drugs with concomitant radiation for rectal cancer.

PURPOSE: Preoperative radiation with combined chemotherapy is effective in shrinking advanced rectal cancer locally and facilitating subsequent surgery. Suppository delivery of 5-fluorouracil is associated with less toxicity and higher rectal tissue concentrations than intravenous administration. This prompted us to evaluate suppository and intravenous administration of 5-fluorouracil and mitomycin C with concomitant radiation to determine associated toxicity. METHODS: Rectal, liver, lymph node, and lung tissue and systemic and portal blood were collected serially from male Sprague Dawley rats to determine drug concentrations following suppository or intravenous delivery of 5-fluorouracil or mitomycin C. Thirty-six animals were randomly assigned to treatment groups and received 5-fluorouracil suppositories, mitomycin C suppositories, or an equivalent intravenous dose of 5-fluorouracil or mitomycin C 30 minutes before radiation therapy. Before and 3, 6, 10, and 15 days following this treatment, blood was collected, colonoscopy was performed, and rectal tissue was harvested for histologic examination. RESULTS: Mitomycin C suppository was significantly less toxic compared with intravenous delivery, and higher rectal tissue concentrations were observed from 10 to 30 minutes (P < 0.05). Compared with intravenous 5-fluorouracil administration and radiation, 5-fluorouracil suppository and radiation resulted in additive myelosuppression at day 6 (P < 0.05) with rapid recovery. CONCLUSIONS: 5-Fluorouracil and mitomycin C suppository delivery combined with radiation causes less systemic toxicity and is more effective than intravenous administration.

Adenocarcinoma↗

PubMed1997

Persistence of penicillin G benzathine in pregnant group B streptococcus carriers.

OBJECTIVE: To determine if streptococcicidal levels of penicillin G benzathine can be detected in maternal serum 4 weeks after treatment with 4.8 million units. METHODS: Thirty-seven pregnant women with positive group B streptococcus vaginal or urine cultures were each given 4.8 million units of penicillin G benzathine. Maternal blood samples were collected after injection and at delivery. Serum penicillin levels were measured by high-pressure liquid chromatography. Follow-up cultures were done when possible. RESULTS: None of the patients had serum penicillin levels below 0.20 microgram/mL 30 days after treatment. Cord blood levels were approximately 50% lower than maternal levels. In all but three subjects, cord blood levels exceeded 0.06 microgram/mL, the minimal inhibitory concentration for group B streptococcus. The three exceptions were patients who delivered more than 100 days after treatment. Group B streptococcus cultures were negative at the time of delivery in 72% of cases. None of the patients with positive cultures were moderately or heavily colonized. CONCLUSION: In pregnant women, penicillin G benzathine levels are high enough to inhibit the growth of group B streptococcus for more than 4 weeks after injection with 4.8 million units. Further studies are needed to evaluate whether this regimen can prevent neonatal colonization and invasive group B streptococcus disease.

Adult↗

PubMed1997

Acylation of human insulin with palmitic acid extends the time action of human insulin in diabetic dogs.

To test whether the binding of insulin to an endogenous serum protein can be used to extend the time action of insulin, human insulin was acylated at the epsilon-amino group of Lys(B29) with palmitic acid to promote binding to serum albumin. Size-exclusion chromatography was used to demonstrate specific binding of the resulting analog, [N(epsilon)-palmitoyl Lys(B29)] human insulin, to serum albumin in vitro, and the time action and activity of the analog were determined in vivo using overnight-fasted, insulin-withdrawn diabetic dogs. In the diabetic animal model, the duration of action of [N(epsilon)-palmitoyl Lys(B29)] human insulin administered intravenously was nearly twice that of unmodified human insulin, and the plasma half-life was nearly sevenfold that of the unmodified protein. Administered subcutaneously, [N(epsilon)-palmitoyl Lys(B29)] human insulin had a longer duration of action; a flatter more basal plasma insulin profile; and a lower intersubject variability of response than the intermediate-acting insulin suspension Humulin L (Lilly, Indianapolis, IN). These studies support the concept that modification of insulin to promote binding to an existing serum protein can be used to extend the time action of human insulin. In addition, the time action, pattern, and decreased variability of response to [N(epsilon)-palmitoyl Lys(B29)] human insulin support the development and further testing of this soluble insulin analog as a basal insulin to increase the safety of intensive insulin therapy.

Acylation↗

PubMed1996

Skin storage.

Explore the source record for details and available documents.

Cryopreservation↗

PubMed1996

Characterization of 4-aminobiphenyl-hemoglobin adducts in maternal and fetal blood-samples.

The maternal-fetal exchange of the potent tobacco-related human carcinogen 4-aminobiphenyl was studied in women smokers during pregnancy. The number of cigarettes smoked per day by each of the women in the study was assessed via questionnaire and by measurement by immunoassay of serum and urine cotinine in maternal and fetal blood samples. Maternal and fetal blood samples were classified as coming from nonsmokers (n = 74), individuals smoking less than 1 pack of cigarettes per day (n = 16), individuals smoking 1 pack of cigarettes per day (n = 19), individuals smoking 1-2 packs of cigarettes per day (n = 19), and individuals smoking greater than 2 packs of cigarettes per day (n = 20). Both maternal and fetal blood samples were obtained at the time of delivery. 4-Aminobiphenyl was extracted from both maternal and fetal blood samples using organic extractions and the released amine was qualitatively and quantitatively characterized by analysis of the samples by gas chromatographic and mass spectrometric analysis. Background levels of 4-aminobiphenyl-hemoglobin adducts were detected in maternal nonsmokers (18.3 +/- 12.7 pg 4-aminobiphenyl/g hemoglobin, mean +/- SD) and in fetal samples (8.88 +/- 5.8 pg/g hemoglobin). Increasing levels of 4-aminobiphenyl-hemoglobin adducts were found as the smoking status of the women increased, ranging from 144 +/- 22.2 ( < 1 pack/d) to 633 +/- 87.9 ( > 2 packs/d). A corresponding increase in the presence of fetal 4-aminobiphenyl-hemoglobin adducts was also detected (74 +/- 17.8, < 1 pack/d, to 319 +/- 50.5, > 2 packs/d). This study confirms that the potent tobacco-related carcinogen 4-aminobiphenyl crosses the human placenta and binds to fetal hemoglobin in significantly higher concentrations in smokers when compared to nonsmokers.

Aminobiphenyl Compounds↗

PubMed1996

HPLC and GC/MS determination of 4-aminobiphenyl haemoglobin adducts in fetuses exposed to the tobacco smoke carcinogen in utero.

Maternal-fetal exchange of the potent tobacco-related human carcinogen, 4-aminobiphenyl, was studied in women nonsmokers and in women smokers as well as in the corresponding fetuses during pregnancy. Smoking status of the women in the study was assessed via questionnaire and measurement by immunoassay of serum cotinine in maternal and fetal blood samples. 4-Aminobiphenyl was extracted from both maternal and fetal blood samples using organic solvent extractions and the released amine was qualitatively and quantitatively characterized by analysis of the samples by high pressure liquid chromatography (HPLC) and gas chromatography coupled with mass spectrometry (GC/MS). Background levels (pg 4-aminobiphenyl/g haemoglobin) of 4-aminobiphenyl-haemoglobin adducts were detected in maternal smokers (mean +/- S.D; 29.6 +/- 16.2 (GC/MS); 23.7 +/- 13.5 (HPLC) and in fetal samples (14.0 +/- 6.5 (GCMS); 10.0 +/- 4.6 (HPLC). Elevated levels of 4-aminobiphenyl-haemoglobin adducts were found in maternal smokers (488 +/- 174 (GC/MS); 423 +/- 154 (HPLC). as well as in the corresponding fetal blood samples (244 +/- 91 (GC/MS); 197 +/- 77 (HPLC). This study confirms that a potent tobacco-related carcinogen, 4-aminobiphenyl, crosses the human placenta and binds to fetal haemoglobin in significantly higher concentrations in smokers when compared to nonsmokers.

Aminobiphenyl Compounds↗

PubMed1996

Chromatographic characterization of hemoglobin benzo[a]pyrene-7,8-diol-9,10-epoxide adducts.

The formation of hemoglobin-carcinogen adducts has been detected in carcinogen-treated animals and in human populations. Although polynuclear aromatic hydrocarbons are ubiquitous in the human environment and DNA-aromatic hydrocarbon adducts have been detected in human tissue, the occurrence of hemoglobin-polynuclear aromatic hydrocarbon adducts in humans has not been thoroughly described. In this study we examined the effects of reaction conditions on the extent of in vitro reaction of human hemoglobin and (+) [3H]benzo[a]pyrene-7,8-diol-9,10-epoxide (anti)(BPDE), a metabolite thought to be largely responsible for the carcinogenic effect of benzo[a]pyrene. The chromatographic properties of the resulting hemoglobin-BPDE adducts were examined by conventional DEAE-cellulose ion exchange liquid chromatography and by reversed phase high performance liquid chromatography. Several adducts were formed which were chromatographically resolved from hemoglobin and from the individual globins. Some adducts were basic and some acidic relative to unaltered hemoglobin, suggesting adduct formation by reaction at carboxyl and basic nitrogen groups, respectively. Alteration of the ion-chromatographic properties of the adducts by an ionic sulfhydryl reagent, together with only a moderate effect of pH on the extent of adduct formation, indicated that the adducts were not formed via reaction with the beta 93 cysteine sulfhydryl group. The chromatographic techniques employed may be applicable for the characterization and analysis of other hemoglobin-carcinogen adducts.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1996

In the absence of counterregulatory hormones, the increase in hepatic glucose production during insulin-induced hypoglycemia in the dog is initiated in the liver rather than the brain.

We have previously demonstrated that the liver can release glucose in response to insulin-induced hypoglycemia, despite the absence of glucagon, epinephrine, cortisol, and growth hormone. The aim of this study was to determine whether this is activated by liver or brain hypoglycemia. We assessed the response to insulin-induced hypoglycemia in the absence of counterregulatory hormones in overnight-fasted conscious adrenalectomized dogs that were given somatostatin and intraportal insulin (30 pmol x kg(-1) x min(-1)) for 360 min. Glucose was infused to maintain euglycemia for 3 h and then to allow limited peripheral hypoglycemia for the next 3 h. During peripheral hypoglycemia, five dogs received glucose via both carotid and vertebral arteries to maintain cerebral euglycemia (H-EU group) concurrently with peripheral hypoglycemia, while six dogs received saline in these vessels to allow simultaneous cerebral and peripheral hypoglycemia (H-HY group). Throughout the study, arterial insulin was 1,675 +/- 295 and 1,440 +/- 310 pmol/l in the H-HY and H-EU groups, respectively. Glucose fell from 6.2 +/- 0.3 to 2.1 +/- 0.0 mmol/l and from 5.8 +/- 0.3 to 1.9 +/- 0.1 mmol/l in the last hour in the H-HY and H-EU groups, respectively (P < 0.05 for both). Norepinephrine rose from 1.12 +/- 0.35 to 2.44 +/- 0.69 nmol/l and from 1.09 +/- 0.07 to 1.74 +/- 0.16 nmol/l in the last hour in the H-HY and H-EU groups, respectively (P < 0.05 for both; no difference between groups). Glucagon, epinephrine, and cortisol were below the limits of detection. The liver switched from uptake to output of glucose during peripheral hypoglycemia in both the H-HY (-7.1 +/- 2.1 to 5.4 +/- 3.1 micromol x kg(-1) x min(-1)) and H-EU (-7.9 +/- 3.5 to 3.4 +/- 1.7 micromol x kg(-1) x min(-1)) groups (P < 0.05 for both; no difference between groups). Alanine levels and net hepatic alanine uptake fell similarly in both groups. There were increases (P < 0.05) in glycerol (12 +/- 3 to 258 +/- 47 micromol/l) and nonesterified fatty acid (194 +/- 10 to 540 +/- 80 micromol/l) levels and in total ketone production (0.4 +/- 0.1 to 1.1 +/- 0.2 micromol x kg(-1) x min(-1)) in the H-HY group, but these parameters did not change in the H-EU group. These data clearly indicate that the lipolytic and hepatic responses to hypoglycemia are driven by differential sensing mechanisms. Thus, during insulin-induced hypoglycemia, when counterregulatory hormones are absent, liver hypoglycemia triggers the increase in hepatic glucose production, whereas cerebral hypoglycemia causes the increases in lipolysis and ketogenesis.

Adrenalectomy↗