Effect of procysteine on aging-associated changes in hepatic GSH and SMase: evidence for transcriptional regulation of smpd3.

In hepatocytes, aging-associated decline in GSH has been linked to activation of neutral SMase (nSMase), accumulation of bioactive ceramide, and inflammation. In this study, we seek to test whether dietary supplementation with the cysteine precursor, L-2-oxothiazolidine-4-carboxylic acid (OTC), would correct the aging-associated differences in hepatic GSH, nSMase, and ceramide. Young and aged mice were placed on a diet that either lacked sulfur-containing amino acids (SAAs) or had 0.

Economics of abdominal wall reconstruction.

The economic aspects of abdominal wall reconstruction are frequently overlooked, although understandings of the financial implications are essential in providing cost-efficient health care. Ventral hernia repairs are frequently performed surgical procedures with significant economic ramifications for employers, insurers, providers, and patients because of the volume of procedures, complication rates, the significant rate of recurrence, and escalating costs. Because biological mesh materials add significant expense to the costs of treating complex abdominal wall hernias, the role of such costly materials needs to be better defined to ensure the most cost-efficient and effective treatments for ventral abdominal wall hernias.

Artificial lung and novel devices for respiratory support.

There is a growing demand for new technology that can take over the function of the human lung, whether it is to assist an injured or recently transplanted lung or to completely replace the native lung. The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation was reported for the first time more than 3 decades ago; nevertheless, its use in lung transplantation was largely abandoned owing to poor patient survival and frequent complications. ECMO as a bridge to lung transplantation has significantly increased during the past 10 years.

Characterization of secretory sphingomyelinase activity, lipoprotein sphingolipid content and LDL aggregation in ldlr-/- mice fed on a high-fat diet.

The propensity of LDLs (low-density lipoproteins) for aggregation and/or oxidation has been linked to their sphingolipid content, specifically the levels of SM (sphingomyelin) and ceramide. To investigate this association in vivo, ldlr (LDL receptor)-null mice (ldlr-/-) were fed on a modified (atherogenic) diet containing saturated fats and cholesterol. The diet led to significantly elevated SM content in all serum lipoproteins.

Clostridium septicum myonecrosis presenting as an acute painful foot.

Spontaneous clostridial myonecrosis (gas gangrene) is an uncommonly encountered presentation of skin and soft-tissue infections with high morbidity and mortality. The diagnosis has been associated with colorectal carcinoma, hematologic malignancies, and diabetes. We report the case of an 81-year-old man who experienced a sudden onset of left ankle and foot pain in association with nonpalpable purpura and hemorrhagic bulla.

Acute alcohol intake impairs lung inflammation by changing pro- and anti-inflammatory mediator balance.

Previous studies have shown that alcohol (ethanol [EtOH]) intoxication impairs lung immunity by affecting cytokines pivotal to the inflammatory process. The objective of this study was to test the hypothesis that acute alcohol intoxication impairs lung innate immunity by downregulating the expression of proinflammatory mediators while simultaneously upregulating anti-inflammatory mediators. EtOH was administered to the mice 0.

Regulation of neutral sphingomyelinase-2 by GSH: a new insight to the role of oxidative stress in aging-associated inflammation.

Oxidative stress and inflammation are fundamental for the onset of aging and appear to be causatively linked. Previously, we reported that hepatocytes from aged rats, compared with young rats, are hyperresponsive to interleukin-1beta (IL-1beta) stimulation and exhibit more potent c-Jun N-terminal kinase (JNK) activation and attenuated interleukin-1 receptor-associated kinase-1 (IRAK-1) degradation. An age-related increase in the activity of neutral sphingomyelinase-2 (NSMase-2), a plasma membrane enzyme, was found to be responsible for the IL-1beta hyperresponsiveness.

Regulation of insulin-like growth factor binding protein-1 expression during aging.

Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is primarily produced in the liver during inflammation and regulates biological activities of IGF-I. Here we demonstrate that interleukin-1beta (IL-1beta) stimulates IGFBP-1 mRNA production in a dose-dependent manner in hepatocytes from Fisher 344 rats. Employment of c-Jun N-terminal kinase (JNK) inhibitor SP600125 resulted in 3-fold reduction of IGFBP-1 mRNA and protein levels, indicating that IL-1beta-induced IGFBP-1 production is mediated through JNK activation.

A multiple-dose phase I study of intranasal hydromorphone hydrochloride in healthy volunteers.

We evaluated the pharmacokinetics, tolerability, and safety of 1 and 2 mg of intranasal hydromorphone hydrochloride in an open-label, single- and multiple-dose study. This Phase I study was conducted in 24 healthy volunteers (13 men and 11 women). Intranasal doses were delivered as 0.

Expression of neutral sphingomyelinase-2 (NSMase-2) in primary rat hepatocytes modulates IL-beta-induced JNK activation.

Neutral sphingomyelinase (NSMase) has been proposed to mediate interleukin (IL)-1beta signaling in liver. In this paper, we used adenovirus-mediated gene transfer to inducibly express FLAG-tagged mouse NSMase-2 in primary rat hepatocytes in order to further elucidate the molecular nature of the NSMase involved. Initial studies confirmed that the EST clone used in these experiments encoded a Mg2+-dependent NSMase.

Pharmacokinetics of butorphanol tartrate administered from single-dose intranasal sprayer.

Purpose: The pharmacokinetics and tolerability of single and multiple doses of intranasal butorphanol tartrate using a single-dose metered sprayer were studied.

Methods: In this randomized, open-label, two-way crossover study, 24 healthy subjects received either 1 or 2 mg of intranasal butorphanol as a single dose (treatment A) and 1 or 2 mg of intranasal butorphanol every six hours for seven doses (treatment B). During phase 1, 12 subjects selected at random received a single 1-mg dose and the other 12 a single 2-mg dose.

Uptake and metabolism of low density lipoproteins with elevated ceramide content by human microvascular endothelial cells: implications for the regulation of apoptosis.

Ceramide is a bioactive molecule involved in cellular responses to stress and inflammation. The major pathway for ceramide accumulation is via agonist-induced activation of cellular sphingomyelinases. It has also been shown that the ceramide level in circulating low density lipoprotein (LDL) increases during systemic inflammation, hence it is of importance to understand whether LDL-derived ceramide also contributes to the cellular ceramide homeostasis and affects cell functions.

A Monte Carlo evaluation of the dosimetric characteristics of the Best Model 2301 125I brachytherapy source.

Recently a new design of a 125I brachytherapy source was introduced for interstitial seed implants, particularly for prostate seed implants. This new source is the Best Model 2301 brachytherapy source. Due to the differences in source design and manufacturing process from one new source to the next, their dosimetric parameters should be determined according to the AAPM TG-43 guidelines.

Early detection and management of COPD. What you can do to reduce the impact of this disabling disease.

Primary care physicians play a pivotal role in the early identification of patients with COPD. Early diagnosis, along with aggressive intervention, is the only way that the increasing morbidity and mortality of COPD can be reversed. Any patient with a history of smoking should undergo evaluation for the possibility of underlying COPD.

Epidermal growth factor protects the liver against alcohol-induced injury and sensitization to bacterial lipopolysaccharide.

Background: Whereas the role of proinflammatory cytokines in the pathogenesis of alcoholic liver disease has been at the forefront of investigation, a possible role for anti-inflammatory cytokines in this disease has received little attention. This study investigated (1) the hepatic protective effect of an anti-inflammatory cytokine, epidermal growth factor (EGF), against deleterious effects of alcohol and sensitization to bacterial lipopolysaccharide (LPS), and (2) the possible mechanisms that underlie such protection.

Methods: Male C57BL/6 mice were fed a Lieber-DeCarli liquid diet that contained alcohol or an isocaloric replacement for 6 weeks.

A role for interleukin-10 in alcohol-induced liver sensitization to bacterial lipopolysaccharide.

Background: Proinflammatory cytokines play an important role in alcohol-induced liver injury. The role of anti-inflammatory cytokines in the initiation and progression of alcoholic liver disease has received little attention. This study tested the hypothesis that an imbalance exists between pro- and anti-inflammatory cytokines in the liver during chronic exposure to alcohol.

Inhibition of caspases in vivo protects the rat liver against alcohol-induced sensitization to bacterial lipopolysaccharide.

Background: The mechanisms of liver sensitization by alcohol to Gram-negative bacterial lipopolysaccharide (LPS) remain elusive. The purpose of this study was two-fold: (1) to test the hypothesis that alcohol-enhanced liver apoptosis may be a sensitizing mechanism for LPS and (2) to further characterize the liver apoptotic response to alcohol.

Methods: Rats were fed a high-fat, alcohol-containing liquid diet for 14 weeks, treated with LPS (1.

Mannose supplementation corrects GDP-mannose deficiency in cultured fibroblasts from some patients with Congenital Disorders of Glycosylation (CDG).

Congenital Disorders of Glycosylation (CDG) are human deficiencies in glycoprotein biosynthesis. Previous studies showed that 1 mM mannose corrects defective protein N-glycosylation in cultured fibroblasts from some CDG patients. We hypothesized that these CDG cells have limited GDP-mannose (GDP-Man) and that exogenous mannose increases the GDP-Man levels.

Pilot study of growth hormone administration during the refeeding of malnourished anorexia nervosa patients.

Objective: In anorexia nervosa (AN), medical stabilization and nutritional repletion are pivotal steps toward physical and psychological recovery. Nutritional stabilization is often difficult in this patient group. Recombinant human growth hormone (rhGH) has been safely used as adjuvant therapy in other groups of malnourished patients.

Technical pitfalls of anterior cruciate ligament surgery.

Anterior cruciate ligament (ACL) reconstruction is extremely common. Although the number of primary reconstructions is increasing, failures and revision procedures continue to occur at approximately the same frequency. ACL reconstruction is a technically difficult procedure, and many failures can be attributed to surgical error.

Purification and characterization of a polyisoprenyl phosphate phosphatase from pig brain. Possible dual specificity.

Microsomal fractions from pig and calf brain catalyze the enzymatic dephosphorylation of endogenous and exogenous dolichyl monophosphate (Dol-P) (Sumbilla, C. A., and Waechter, C.

Critical issues in the evolving management of rectal cancer.

Evolving trends in the management of rectal cancer have focused on organ preservation, improved quality of life, and survival of patients. A significant shift is underway in our thinking about what constitutes the true rectum and defining the "proximal" and "distal" segments of the rectum. Tumor mobility remains a dominant prognostic factor in patient selection and choice of surgery.