Postprandial lipid metabolism and beta-cell function in non-insulin-dependent (type 2) diabetes mellitus after a mixed meal with a high fat content

Postprandial lipid profiles and release of insulin (INS), intact proinsulin (PI), and 32-33 split proinsulin (SPI) in response to a mixed meal with a high fat content were determined over a 12 h period in non-obese control subjects (n = 10) and non-insulin-dependent (Type 2) diabetic (NIDDM) patients with normotriglyceridaemia (NTG; n = 11) and hypertriglyceridaemia (HTG; n = 10), by calculation of the 'areas under the curves' (AUC). The postprandial triglyceride-AUC was significantly greater in HTG-NIDDM patients (p < 0.05) than in NTG-NIDDM or control subjects. Chylomicron clearance was impaired only in HTG-NIDDM patients (p < 0.05). Chylomicron-remnant clearance was impaired in both groups of NIDDM patients (p < 0.05). The postprandial suppression of plasma non-esterified fatty acid (NEFA) content was impaired in HTG-NIDDM patients (p < 0.05). The postprandial INS-, PI- and SPI-AUCS were significantly greater than in the control subjects (p < 0.05). In NIDDM, triglyceride-AUC correlated significantly with PI and SPI release (triglyceride-AUC vs PI, p < 0.05; triglyceride-AUC vs SPI, p < 0.01). Chylomicron AUC was unrelated to the fasting plasma INS, PI or SPI content, unlike chylomicron-remnant-AUC (Chylomicron-remnant-AUC vs INS, p = NS; chylomicron-remnant-AUC vs PI, p < 0.01; chylomicron-remnant-AUC vs SPI, p < 0.01). The NEFA response was associated with fasting plasma SPI content (NEFA-AUC vs SPI, p < 0.05). Postprandial chylomicron AUC was not related to the overall secretion of INS, PI or SPI. However, triglyceride-, chylomicron-remnant- and NEFA-AUCs were all associated positively with the release of PI and SPI (p < 0.05). In multivariate analyses, chylomicron-remnant clearance had the major relationship with the release of insulin precursors, accounting for 23% of the variability (p < 0.01). Inclusion of overall response of free fatty acids improved the model, with both parameters together accounting for 30% of the variability (p < 0.01). The output of the beta-cell over the postprandial period differed between the NIDDM patients and the control subjects in that when glycaemic stimulation was moderate, the proportion of insulin-like molecules as a percentage of the total output was greater than in control subjects but this was not the situation when glycaemia was greatest. We conclude that abnormal postprandial lipaemia in NIDDM is associated with beta-cell output, possibly mediated by the availability of free fatty acids.     

Experiences with percutaneous endoscopic gastrostomy

Today the procedure of choice for long-term enteral tube feeding in patients with prolonged swallowing difficulties or inabilities is percutaneous endoscopic gastrostomy (PEG). The primary indications are head and neck cancers, neurologic dysphagia, cancer cachexia, and obstruction of the esophagus and pharynx with enough space for an endoscopic procedure. This technique requires no general anesthesia and is possible in patients with contraindications to surgical gastrostomy. Between September 1994 and April 1995 a total of 115 patients underwent PEG placement attempts. We employed the pull-technique with 15-Freka PEG tubes. The average procedure time, including esophagogastroduodenoscopy, was 17 minutes. In nine cases PEG insertion was impossible owing to severe obstruction of the esophagus. In 46 (40%) patients local abdominal pains started on the first or second postoperative day; 7 of these patients required surgical consultation, and no further intervention was needed. In only one patient was there a serious complication that required surgical intervention: a presumed perforation that turned out to have no correlate upon review. All patients received single-shot antibiotic prophylaxis; and only in those patients with abdominal symptoms do we recommend a prolonged antibiosis. The abdominal symptoms reported were due to a slight leak of gastric fluid causing a topical peritonitis, which required no further treatment. In our experience PEG is a useful alternative to surgical gastrostomy. The simplicity of this procedure leads to low complication rates, short hospitalization, and is possible on an outpatient basis. It is cost-efficient and has a much better psychological tolerance than nasogastric tubes.     

Behavior and the law reconsidered: psychological syndromes and profiles

Three months after facial nerve transection, total numbers of motoneurons in the facial nucleus of six month (adult) Fischer 344 and Wistar rats were reduced to 83% and 75% of contralateral values, respectively (P < 0.05). This procedure in 22-26 month (ageing) Fischer 344 rats and Wistar rats resulted in a reduction of motoneuron numbers to 77% and 60% of the respective contralateral values (P < 0.05). Compared to adults, contralateral facial nuclei of aging Fischer 344 rats contained 10% fewer motoneurons (non-significant), while ageing Wistar rats had 22% fewer (P < 0.05). No significant changes were found in the proportion of surviving motoneurons expressing calcitonin gene-related peptide, galanin, receptor tyrosine kinase-C or the alpha subunit of the ciliary neurotrophic factor receptor. We conclude that ageing reduces facial motoneuron number and increases their vulnerability to axotomy in Wistar rats, but not in Fischer 344 rats. In neither strain, however, does the proportion of surviving motoneurons expressing the above neuropeptides or neurotrophic factor receptors change. This information may be relevant to those hypotheses of age-related neuronal degenerations which assume that decreased neurotrophic support renders ageing neurons more vulnerable to injury.     

Restricted growth potential of rat neural precursors as compared to mouse

The HLA class II alleles were analyzed by the PCR-SSP technique in the DNA samples obtained from 27 Thai patients with non Hodgkin's lymphoma (NHL). It was found that (1) the incidence of HLA-DRB1*15 and HLA-DRB1*09 was slightly decreased (P > 0.05). On the other hand, the incidence of HLA-DQB1 alleles was the same as control. However, further study is suggested in order to conclude the close relationship between the presence of certain HLA class II alleles and susceptibility to NHL in Thai patients.     

Diagnosis of infectious diseases: a cytopathologist's perspective

This review explores the role of the cytopathology laboratory in the detection and presumptive identification of microorganisms. Sample procurement by exfoliation, abrasion, and aspiration techniques, as well as a variety of cytopreparatory and staining methods, is reviewed. Emphasis is placed on the utility of fine-needle aspiration as a rapid, safe, and cost-effective diagnositic procedure. The role of rapid interpretation and specimen triage is also discussed. Cytomorphologic features and staining characteristics are presented for a spectrum of microorganisms potentially encountered in the cytopathology laboratory. Pitfalls in diagnosis and the usefulness of special stains and ancillary techniques are also evaluated. The importance of communication, collaboration, and clinical correlation is stressed.     

Thiol activation of endopeptidase EC 3.4.24.15. A novel mechanism for the regulation of catalytic activity

Endopeptidase EC 3.4.24.15 (EP24.15) is a thermolysin-like metalloendopeptidase involved in the regulated metabolism of a number of neuropeptides. Unlike other thermolysin-like peptidases EP24.15 displays a unique thiol activation, a mechanism that is not clearly understood. In this study we show that both recombinant and tissue-derived EP24.15 are activated up to 8-fold by low concentrations (0.1 mM) of dithiothreitol. Additionally, under non-reducing conditions, recombinant and native EP24.15 forms multimers that can be returned to the monomeric form by reduction. We have also shown that competitive inhibitor binding occurs only to the monomeric form, which indicates that catalytic site access is restricted in the multimeric forms. Through systematic site-directed mutagenesis we have identified that cysteine residues 246, 253, and possibly 248 are involved in the formation of these multimers. Furthermore, both a double mutant (C246S/C253S) and a triple mutant (C246S/C248S/C253S) are fully active in the absence of reducing agents, as measured by both inhibitor binding and hydrolysis. The formation and disruption of disulfide bonds involving these cysteine residues may be a mechanism by which EP24.15 activity is regulated through changes in intra- and extracellular redox potential.     

Dynamics of biomolecules: assignment of local motions by fluorescence anisotropy decay

Many biological systems have multiple fluorophores that experience multiple depolarizing motions, requiring multiple lifetimes and correlation times to define the fluorescence intensity and anisotropy decays, respectively. To simplify analyses, an assumption often made is that all fluorophores experience all depolarizing motions. However, this assumption usually is invalid, because each lifetime is not necessarily associated with each correlation time. To help establish the correct associations and recover accurate kinetic parameters, a general kinetic scheme that can examine all possible associations is presented. Using synthetic data sets, the ability of the scheme to discriminate among all nine association models possible for two lifetimes and two correlation times has been evaluated. Correct determination of the association model, and accurate recovery of the decay parameters, required the global analysis of related data sets. This general kinetic scheme was then used for global analyses of liver alcohol dehydrogenase anisotropy data sets. The results indicate that only one of the two tryptophan residues in each subunit is depolarized by process(es) independent of the enzyme's rotations. By applying the proper kinetic scheme and appropriate analysis procedures to time-resolved fluorescence anisotropy data, it is therefore possible to examine the dynamics of specific portions of a macromolecule in solution.     

Modern medical electricity in the management of pain

With the economics of medical care and the history of electrotherapeutics firmly in mind, one should seek treatments that are efficient and effective. There is no question that relief of the symptom of pain must be a primary focus of treatment, whether or not a specific pathology is known. Electric devices may be justifiably used for their placebo effects, if the cost is reasonable, because side effects are minor and infrequent. Research shows specific neurochemical effects of several electrotherapeutic devices, supporting the notion that specific therapeutic effects exist in addition to placebo effects. Passage of time and further research will determine which of the current techniques and devices will find their way into future similar articles or monographs.     

Decrease of manganese superoxide dismutase activity in rats fed high levels of iron during colon carcinogenesis

Diets high in fat or iron have been associated with an increased risk for development of colon cancer. These two dietary factors are known to decrease manganese superoxide dismutase (MnSOD) activity in colonic mucosa. MnSOD is an antioxidant enzyme that protects mitochondria from oxygen radical damage. MnSOD has tumour suppressive activity and is absent or decreased in most tumours, including those from the colon. This study was designed to determine the effects of high dietary lipid and iron levels on MnSOD activity during the early weeks of colon carcinogenesis. Male Fischer-344 rats were fed 20% lipid diets of either corn oil or menhaden oil containing adequate iron (35 mg/kg) or supplemental iron (535 mg/kg). Rats from each diet were divided into carcinogen treatment groups and given two weekly injections of either azoxymethane (AOM) at a dose of 12 mg/kg, or saline. Mucosal tissue was collected 1, 6 and 12 wk following injections and analysed for MnSOD activity, mineral concentration and nuclear aberrations. Results showed that iron supplementation increased nuclear aberrations, and decreased manganese concentration and MnSOD activity in colonic mucosa ot control animals. AOM, and interaction of iron and AOM, also decreased MnSOD activity. A decrease in the activity of this enzyme during carcinogenesis may be one mechanism whereby these dietary factors ultimately increase tumour risk.