Mary Ann Emanuele

Hepatic Apoptosis and Proliferation in Male and Female Rats Fed Alcohol: Role of Cytokines

BACKGROUND The female liver is more sensitive to the toxic effect of chronic alcohol intake than the male liver. The aim of the study was to compare the influence of gender and sex hormonal status on apoptosis and cell proliferation following chronic ethanol intake. METHODS Male and female rats were pair fed for 8 weeks a liquid diet containing 36% of their total daily calories as ethanol (ETOH group) or sucrose (control group). Liver samples were analyzed for apoptosis and hepatocyte proliferation by immunohistochemistry. The hepatic production of factors able to influence cell death and proliferation, such as tumor necrosis factor alpha (TNFalpha) and interleukin 6 (IL-6) were determined. RESULTS In both male and female rats, ethanol intake promoted apoptosis in the liver. This effect of ethanol was more evident in female than male rat livers. Hepatic TNFalpha levels, which promote apoptosis, are significantly more elevated in female than in male livers. Hepatic IL-6 production, which promotes hepatocyte proliferation, was induced by ethanol only in males, but not female animals. CONCLUSION This observed difference in cytokine responses may contribute to the enhanced sensitivity of female liver to EtOH-induced injury.

Adverse Clinical Outcomes Associated With Elevated Blood Alcohol Levels at the Time of Burn Injury

Elevated blood alcohol content (BAC) on admission is associated with poorer outcomes, larger burns and more inhalation injury. This study’s purpose was to examine the effects of alcohol through a matched case-controlled study, measuring early and extended markers of clinical outcomes. The hypothesis was that patients with an elevated admission BAC would require more resuscitation and have a longer hospital stay. Admissions 16 to 75 years of age with 15 to 75% TBSA and admission BACs were identified. Patients with BAC >30 mg/dl (BAC+, cases) were matched with patients with undetectable BAC (BAC−, controls), according to age, sex, TBSA, inhalation injury and mechanism. Screening identified 258 patients, 146 with admission BACs. Twenty-seven had a BAC ≥ 30 mg/dl. There were 24 matched pairs. At 24 hours, BAC+ group had larger acute physiology and chronic health evaluation II scores (23.33 vs 18.75, P < .05), fluid requirements (5.25 vs 3.82 L (cc/kg/TBSA), P < .05), and base deficit (11.15 vs 7.15, P < .05). The duration of mechanical ventilation (14.85 vs 4.23 days, P < .05), intensive care unit length of stay (22.85 vs 9.38, P < .05), hospital length of stay (28.95 vs 15.68, P < .05), and mean hospital charges (

A randomized trial of two weight-based doses of insulin glargine and glulisine in hospitalized subjects with type 2 diabetes and renal insufficiency.

239,507 vs

Coupled reverse transcription-polymerase chain reaction (RT-PCR) technique is comparative, quantitative, and rapid: uses in alcohol research involving low abundance mRNA species such as hypothalamic LHRH and GRF.

144,598, P < .05) were increased in the BAC+ patients. Despite matched baseline injury characteristics, elevated BAC was associated with poorer short term and extended clinical outcomes, illustrating the impact of alcohol intoxication on physiologic derangement after burn injury.

Vitamin D and Diabetes : Let the Sunshine In

OBJECTIVE Renal insufficiency may increase the risk of hypoglycemia in hospitalized patients with diabetes who are treated with insulin. We randomized inpatients with type 2 diabetes and chronic renal failure to treatment with two different dose levels of insulin glargine and glulisine and studied control of hyperglycemia and the frequency of hypoglycemia. RESEARCH DESIGN AND METHODS We conducted a multicenter, prospective, randomized trial to compare the efficacy of once-daily glargine and three-times daily glulisine at 0.5 vs. 0.25 units/kg/day. A total of 107 subjects had type 2 diabetes for >1 year, had a glomerular filtration rate <45 mL/min but did not require dialysis, and had an initial blood glucose (BG) >180 mg/dL. Doses were adjusted based on four-times daily BG measurements for 6 days. RESULTS Mean BG on the first day was 196 ± 71 mg/dL in the group receiving 0.5 units/kg (0.5 group) and 197 ± 55 mg/dL in the group receiving 0.25 units/kg (0.25 group; P = 0.94). On days 2 to 6, mean BG was 174 ± 52 mg/dL in the 0.5 group and 174 ± 46 mg/dL in the 0.25 group (P = 0.96). There were no significant differences between groups in the percentage of BG values within the target range of 100 to 180 mg/dL on any of the 6 study days. In the 0.5 group, 30% experienced hypoglycemia (BG <70 mg/dL) compared with 15.8% of the 0.25 group (P = 0.08). CONCLUSIONS Reduction of initial glargine/glulisine insulin weight-based dosing in hospitalized patients with diabetes and renal insufficiency reduced the frequency of hypoglycemia by 50% without compromising the control of hyperglycemia.

Effect of a hypoglycemic episode on neuropsychological functioning in diabetic children.

The measurement of alterations in low abundance mRNAs such as the hypothalamic hormones luteinizing hormone-releasing hormone (LHRH) and growth hormone-releasing hormone (GHRH or GRF) from individual hypothalamic tissues in rats has previously been difficult and usually required either isolation of poly(A) mRNA or the pooling of numerous animals to obtain a reasonable signal on Northern blots. Although more sensitive detection methods exist, such as the use of RNA probes or solution hybridization (RNase protection), we have found the most reliable, sensitive, rapid, and accurate method is the reverse transcription-polymerase chain reaction (RT-PCR) using histone H3.3 as an internal control for both steps of this procedure. H3.3 is a cell-cycle independent and constitutively expressed gene in all tissues. We have developed an RT-PCR assay for LHRH and GRF mRNA quantitation and comparative analysis for hypothalamic and extrahypothalamic brain tissues and present the use of RT-PCR for LHRH quantitation in ethanol (EtOH) studies.

Bridge over troubled waters: Safe and effective transitions of the inpatient with hyperglycemia

Diabetes is a leading cause of cardiovascular disease. Persons with diabetes are at greater risk for early cardiac mortality, and for repeat events if they survive their first cardiac event. Recently, low serum concentrations of vitamin D have been associated with increased risk for cardiac events. Evidence indicates that persons with diabetes have lower serum concentrations of vitamin D. In addition, persons at risk for diabetes or metabolic syndrome have inadequate serum concentrations of vitamin D. This review will assess the evidence relative to the impact of vitamin D in the development of diabetes, metabolic syndrome, and diabetes complications. Studies that address vitamin D and its impact on metabolic outcomes as well as possible mechanisms of action are provided. Finally, the assessment and suggested treatment for vitamin D deficiency is addressed. Effective detection and treatment of inadequate vitamin D concentrations in persons with diabetes or those at risk for diabetes may be an easy and cost-effective therapy which could improve their long-term health outcomes as well as their quality of life.

Peripubertal paternal EtOH exposure

The present study investigated neuropsychological functioning in school-age children at various points in time surrounding a hypoglycemic episode using 13 tasks drawn from age-appropriate, standard neuropsychological tests. The results demonstrate the effects of a hypoglycemic episode on neuropsychological functioning even after detectable physical symptoms have subsided. Although we are unable to delineate clearly their temporal course, it appears that the impact of such episodes is transient. In general, the pattern exhibited by these children who have presumably recovered from their mild hypoglycemic episode involved reduced motor performance, attention, and memory. The observed prolonged recovery time of these functions presents important implications for the child in both school and social settings.

Alendronate administration and skeletal response during chronic alcohol intake in the adolescent male rat.

4 Department of Medicine, Division of General Internal Medicine, Hospitalist Program, University of California, Irvine, Irvine, California. P rofessional and patient safety organizations have recognized the importance of safe transitions as patients move through the health care system, and such attention is even more critical when attempting to achieve glycemic control. Since the publication of the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS), we have known that intensive glycemic control in the ambulatory setting prevents complications in both type 1 and type 2 diabetes mellitus (DM). Despite the increased risk of hypoglycemia, these trials changed practice patterns in the outpatient settings in favor of intensification of diabetes therapy. In the same way, randomized, prospective trials using intravenous (IV) insulin therapy have revolutionized our thinking about inpatient care by showing that tight glycemic control in the critically ill and patients with acute myocardial infarction reduces mortality and morbidity. These, as well as additional observational studies associating hyperglycemia with poor outcomes in a variety of medical and surgical patients, have led to increased attention on glycemic control in all venues of care. Concerns over excessive hypoglycemia and a nonsignificant increase in mortality in certain populations of medical intensive care unit (ICU) patients have raised questions over whether the initial studies can be reproduced or generalized to other groups of inpatients. Additional studies are underway to clarify these questions but consensus exists that blood glucose values should at least be less than 180 mg/dL and that the traditional practice of ignoring hyperglycemia is no longer acceptable. While a uniform focus on glycemic control will allow our patients to receive a consistent message about diabetes, the unique limitations inherent to each practice setting requires different therapeutic regimens and intentional focus on the risks as patients transition from one care area to another. This work addresses several areas of care transition that are particularly important in safely achieving glycemic control including: transition into the hospital for patients on a variety of home regimens, transitions within the hospital (related to changes in dietary intake, change from IV to subcutaneous [SC] therapy, and the perioperative setting), and the transition from the hospital to home or another healthcare facility.

In vivo effects of acute EtOH on rat α and β luteinizing hormone gene expression

Fetal alcohol syndrome usually implies effects on the offspring of maternal EtOH consumption during gestation, with fewer reports addressing the impact of paternal exposure on the progeny. One previous report has dealt with the impact of EtOH exposure on peripubertal male rats as a model of teenage drinking and the deleterious effects on the offspring. We report here findings examining the effect of 2 mo of EtOH feeding on male animals as they progressed through puberty on their ability to impregnate EtOH-naive female rats and characteristics of the subsequent litters. The EtOH-imbibing fathers weighted significantly less than pairfed controls and animals ingesting a non-EtOH liquid diet ad libitum. Nevertheless, they were able to mate successfully, although fecundity was significantly reduced. The number of successful pregnancies, defined as carried to term, was diminished from 92% in controls to 75% in EtOH-fed animals (p<0.05). There was increased paternal testicular oxidative injury demonstrated by enhanced lipid peroxidation, protein oxidation, and decreased ratio of reduced to oxidized glutathione. The litter size of the EtOH-exposed males was reduced by 46%. The average litter size was 12.4±1.5 pups/litter in ad libitum animals, virtually identical to the 12.5±0.6 pups/litter in the pair fed controls. This is in sharp contrast to the 6.7±0.1 pups/litter from the paternal EtOH matings (p<0.001). There was an increase in the average individual weight of pup offspring of paternally EtOH-exposed animals (p<0.01 vs pair-fed controls and p<0.05 vs ad libitum). Curiously, the male-to-female pup ratio was altered with a higher preponderance of male offspring from EtOH-fed fathers. There were no gross malformations noted among the pups. Insulin-like growth factor-1 levels in the pups at 10 d of age were unaltered between the groups. However, leptin was significantly elevated in the EtOH offspring. It appears that chronic EtOH exposure in the peripubertal fathers subsequently decreases fecundity and that this may be mediated by testicular oxidative injury, perhaps leading to accelerated germ cell apoptosis.