Inhibition of hepatic glucose production by SDZ 51641

The new oral hypoglycemic agent SDZ 51641 was evaluated in nondiabetic rats and a rat model of human non-insulin-dependent diabetes mellitus. Diabetes was induced with a single injection of 37.5 mg/kg streptozocin, and the rats exhibited hyperglycemia in the fed state with normal insulin levels. Treatment of nondiabetic animals with 100 mg/kg SDZ 51641 given orally significantly decreased serum glucose and ketone levels within 4 h without affecting insulin levels. Nonesterified fatty acids increased more than twofold during the same period. Its effect on ketone and fatty acid levels suggests that SDZ 51641 acts as an inhibitor of fatty acid oxidation. Diabetic rats treated with SDZ 51641 exhibited a significant acute hypoglycemic response, which was more pronounced after 3 days of treatment. The compound also significantly decreased serum cholesterol and triglyceride levels 27 and 53%, respectively. When endogenous hepatic glucose production was assessed in nondiabetic and diabetic animals via continuous infusion of [3-3H]glucose, we found that hepatic glucose production was elevated 43% in diabetic compared with control animals. When diabetic rats were treated with 100 mg/kg SDZ 51641, hepatic glucose production decreased to normal levels within 6 h. Hyperinsulinemic-euglycemic clamp studies indicated that SDZ 51641 had no effect on insulin-stimulated glucose utilization. Measurement of [1-14C]oleate oxidation in isolated hepatocytes demonstrated that SDZ 51641 inhibited long-chain fatty acid oxidation in a concentration-dependent manner. The compound was ineffective at inhibiting long-chain fatty acid oxidation in epitrochlearis or soleus muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

CHARACTERISTICS OF MEMBRANE TRANSPORT PROCESSES OF MACULA DENSA CELLS

1. Macula densa (MD) cells are located within the thick ascending limb (TAL) and have their apical surface in contact with tubular fluid and their basilar region in contact with the glomerulus. These cells sense changes in luminal fluid sodium chloride concentration ([NaCl]) and transmit signals resulting in changes in vascular resistance (tubuloglomerular feedback) and renin release. 2. Current efforts have focused on understanding the cellular transport mechanisms of MD cells. Progress in this area has benefited from the use of the isolated perfused TAL-glomerular preparation, which permits direct access to MD cells. 3. Using microelectrodes to measure basolateral membrane potential (V_BL) of MD cells, it was found that VBL was very sensitive to changes in luminal fluid [NaCl]. As [NaCl] was elevated from 20 to 150mmol/L, V_BL was found to depolarize by over 30 mV. 4. Basolateral membrane potential measurements were also used to identify an apical Na⁺: 2CI^?: K⁺ cotransport pathway in MD cells that is the major pathway for NaCl entry into these cells. 5. Other work identified a basolateral chloride channel that is presumed to be responsible for changes in V_BL during alterations in luminal [NaCl]. This channel, which is the predominant conductance across the basolateral membrane, may be regulated by intracellular Ca²⁺ and cAMP. 6. An apical Na⁺: H⁺ exchanger in MD cells was detected by measuring changes in intracellular pH using the fluorescent probe 2′,7′-bis-(2-carboxyethyl)-5(and-6) carboxyfluorescein. 7. Using patch-clamp techniques, a high density of pH- and Ca²⁺-sensitive K⁺ channels was observed at the apical membrane of MD cells. 8. Other studies found that, at the normal physiological conditions prevailing at the end of the TAL (luminal [NaCl] of 20–60 mmol/L), reabsorption mediated by MD cells is very sensitive to changes in luminal [NaCl].     

Utilization and clinical manifestations of human immunodeficiency virus type 1-infected children presenting to a pediatric emergency department

A retrospective review was conducted of 22 human immunodeficiency virus type 1 (HIV-1)-infected children under 13 years of age presenting to an inner city pediatric emergency department to determine their clinical manifestations of disease and utilization of emergency department services. When compared with a population of 78 normal children, the infected children were more likely to present with cough, difficulty in breathing, and lethargy. Pneumonia, diarrhea, and dehydration were more common diagnoses in the infected children, who were more likely to be admitted, had more invasive procedures, and required more professional staff to provide care. There was no significant difference in the frequency of visits (visits/month of age) when comparing the two groups. As expected, the infected children presented with problems associated with pediatric HIV-1 infection. Our results suggest that HIV-1-infected children require an increased level of care in the emergency department and subsequent admission to the hospital. These children did not visit the emergency department more frequently than the controls. This may be the result of an active outpatient HIV clinic in our hospital, which is available to both scheduled and unscheduled patients.     

Weekly subcutaneous recombinant human erythropoietin corrects anemia of progressive renal failure

PURPOSE: The purpose of this study was to analyze data retrospectively from our use of weekly subcutaneous recombinant human erythropoietin (rHuEPO) in predialysis and peritoneal dialysis patients with anemia. PATIENTS AND METHODS: All anemic patients with progressive renal failure (12 predialysis and seven home peritoneal dialysis) in whom subcutaneous rHuEPO therapy was begun at, or was reduced to, a weekly dose were studied retrospectively. Patients were not selected for, nor excluded from, these observations for any other reason. Hematocrit and endogenous creatinine clearance were monitored regularly, and no other new treatment for anemia was given except oral iron. Iron-deficiency anemia was considered improbable because of normal red blood cell mean corpuscular volume. Unfortunately, iron parameters were not monitored. RESULTS: The hematocrit increased 4 to 9 percentage points in 4 to 13 weeks in all but two patients who were initially treated with weekly doses, and a hematocrit of 31% was achieved in these patients within 6 to 12 weeks. The mean effective dose to accomplish this was 150 U/kg. All but three patients could be maintained on weekly doses at a hematocrit of 31% or higher. The mean effective dose was 75 U/kg. CONCLUSION: It is concluded that subcutaneous rHuEPO administered weekly can correct the anemia of predialysis and peritoneal dialysis patients. Weekly dosing is more convenient for patients and may be less costly for Medicare providers.     

Narrative and procedural discourse in temporal lobe epilepsy.

It is well established that some individuals with temporal lobe epilepsy (TLE) demonstrate language deficits at the single word level. However, discourse production rarely has been examined quantitatively within this group. This study compared adult TLE patients with an early seizure onset (< or = age 14 years, n = 27) to a control group (n = 28) on narrative and procedural discourse tasks. As a group, the TLE patients performed normally on the procedural discourse task, but differed significantly from the controls on several narrative discourse variables. At the individual level, 30% of the TLE patients versus 4% of the controls demonstrated impaired discourse ability (p and 0.01). Within this early onset TLE group, discourse performance was not associated with demographic or seizure history variables. Considering the cognitive domain, discourse performance correlated significantly with working memory. In summary, mild discourse dysfunction was present in a significant minority of early onset TLE patients, but this deficit was not closely associated with other language measures. Discourse ability and its neuropsychological, neuroanatomical and conversational speech correlates deserve further study in TLE patients.     

Comparison of three oral sip-feed supplements in patients with cancer

This study set out to compare the long-term palatability of three oral sip-feed supplements. Sixty patients with various malignancies were randomized to receive one of three products—Build-Up, Fortimel and Fortisip. Participants were encouraged to take as much of the supplements each day for as long as they could manage. At the initial tasting, palatability and acceptability of the products was recorded and this was repeated throughout the trial period. Patients' reasons for discontinuing the trial were noted.
Build-Up was found to be the best-tolerated product of the three. It was taken for a significantly longer time than either Fortimel or Fortisip. There was an indication that Build-Up was more acceptable at the initial tasting than Fortisip but not Fortimel. A smaller proportion of patients stopped taking Build-Up due to flavour-related reasons compared to Fortisip but there was no significant difference between Build-Up and Fortimel. In all, 54% of the patients discontinued the trial for flavour-related reasons. Thirty-five per cent found that the sip-feeds they had been allotted unpalatable at the initial tasting, while 19% stopped the trial due to 'flavour fatigue'. Only 10% of the sample continued taking their allotted product for 90 days or more.     

Developing nurse practitioners to develop practice: the experiences of nurses working on a Nursing Development Unit

Aim To elicit nurses' accounts of their involvement with nursing research and their interpretations of the meaning of these projects for their practice.
Background The links between research and practice development in health care are poorly understood and require further exploration in the light of the emerging research and development agenda within the National Health Service.
Methods Semi-structured interviews were conducted with 15 qualified nurses working on a Nursing Development Unit. The interviews were tape recorded, transcribed and analysed thematically.
Findings Data analysis identified two distinct groups—a core group of nurses actively engaged in the research projects and a peripheral group involved in data collection. The characteristics of the core group mirror the characteristics of those involved in non-research-based practice development activities.
Conclusions Engaging in research activities does not always result in the development of practice, however, there appears to be a link between practice development and critical thinking.     

The inhibition of the oxidation of low density lipoprotein by (+)-catechin, a naturally occurring flavonoid.

(+)-Catechin inhibited the copper-catalysed oxidation of human low density lipoprotein (LDL) in a dose-dependent manner with complete inhibition at 20 micrograms/mL. The flavonoid at a concentration of 50 micrograms/mL also inhibited oxidation of LDL induced by the mouse transformed macrophage J774, human monocyte-derived macrophages and vascular endothelial cells isolated from human umbilical cords. LDL modified by copper-catalysed or cell-induced oxidation was endocytosed and degraded by human macrophages at a much greater rate than native LDL. LDL reisolated from copper or cell incubations in the presence of (+)-catechin was endocytosed and degraded at rates similar to native LDL. (+)-Catechin appeared to inhibit the uptake and degradation by macrophages of cell-modified LDL. The actions of (+)-catechin on cell-induced oxidation of LDL are consistent with the ability of flavonoids of similar structure to inhibit lipoxygenases and with a role for lipoxygenases in cell-induced modification of LDL in vivo.