The effect of an antibacterial washing-up liquid in reducing dishwater aerobic plate counts.

AIMS: To assess any significant differences in the aerobic plate count (APC) of catering dishwaters following the use of a traditional, nonantibacterial or an antibacterial washing-up liquid. METHODS AND RESULTS: A dishwashing trial was undertaken within a commercial restaurant of 6 weeks duration (3 weeks with each washing-up liquid in a randomized, weekly pattern). Five replicate samples were taken from the dishwater at the end of the washing-up operation, on three separate occasions each day corresponding to mid-morning, lunchtime and mid-afternoon meal preparations. CONCLUSIONS: The antibacterial product was shown to significantly reduce the APC by an average log10 reduction of 1.81 CFU ml(-1) (98.5%) as compared with the traditional product. APC were lower for each of the three weekly time periods for the antibacterial product. Continued use of the antibacterial product did not decrease the APC of the dishwater, though with the traditional product, dishwater counts increased throughout the trial week. SIGNIFICANCE AND IMPACT OF THE STUDY: Antibacterial washing-up liquids, with proven activity in controlling levels of microorganisms in dishwaters, could play a significant role in reducing the risk of cross-contamination between washed articles during washing-up operations.

Estrogen-induced changes in IGF-I, Myb family and MAP kinase pathway genes in human uterine leiomyoma and normal uterine smooth muscle cell lines.

Many studies have implicated numerous hormones, growth factors, cytokines and other signal transduction molecules in the pathogenesis of uterine leiomyoma. Estrogen and estrogen-related genes are thought to play a key role in the growth of uterine leiomyomas, but the molecular mechanisms are unclear. In an attempt to investigate various pathways that might be involved in estrogen-regulated uterine leiomyoma growth as well as to identify any novel effector genes, microarray studies comparing estrogen-treated uterine leiomyoma cells (UtLM) and normal myometrial cells to untreated cells were performed. Several genes were differentially expressed in estrogen treated UtLM cells, including insulin-like growth factor-I (IGF-I) and others potentially involved in the IGF-I signalling pathway, specifically genes for A-myb, a transcription factor which promotes cell cycle progression and for MKP-1, a dual specificity phosphatase that dephosphorylates mitogen-activated protein kinase. IGF-I and A-myb were up-regulated in estrogen-treated cells while MKP-1 was down-regulated. Two other cell cycle promoting genes, c-fos and myc, were also down-regulated in estrogen treated UtLM cells. These genes are typically up-regulated in response to estrogen in some cells, notably breast epithelial cells, yet consistently have lower expression levels in uterine leiomyoma tissue when compared to autologous myometrium. Our results demonstrate some novel genes that may play a role in the growth of uterine leiomyoma, strengthen the case for involvement of the IGF-I pathway in the response of UtLM to estrogen and corroborate evidence that uterine smooth muscle cells respond to estrogen with a different gene expression pattern than that seen in epithelial cells.

The microbial ecology of high-risk, chilled food factories; evidence for persistent Listeria spp. and Escherichia coli strains.

AIMS: The intention of this study was to provide evidence of any Listeria spp. or Escherichia coli strain persistence, and to identify whether strains of these organisms adapt to specific environmental or product niches in food factories. METHODS AND RESULTS: A 3-year assessment of the microbial ecology of four, ready-to-eat food-processing factories was undertaken in which approx. 196 000 and 75 000 product and environmental samples were examined for Escherichia coli and Listeria spp. respectively. A total of 152 E. coli isolates (44 environmental and 108 product in 62 ribogroups) and 260 Listeria spp. isolates (174 environmental and 86 product in 30 ribogroups) were identified and ribotyped. The overall prevalence of E. coli (0.08%), all Listeria spp. (0.35%) and L. monocytogenes (0.23%) was very low. Some 10 E. coli ribogroups and 14 Listeria spp. ribogroups showed evidence for persistence, defined as the isolation of the same strain, from the same site, over a prolonged time period. The majority of E. coli strains were product niche oriented whilst the majority of Listeria spp. strains were environmental niche oriented. CONCLUSION: Current UK high-risk food factory designs, personnel hygiene and cleaning and disinfection regimes are sufficient to control Listeria spp. and E. coli to very low levels. SIGNIFICANCE AND IMPACT OF THE STUDY: Persistent strains of these organisms, however, can remain within factory high-risk production areas over considerable time periods, warranting an examination of the strain persistence mechanisms and alternative hygiene controls.

Biocide use in the food industry and the disinfectant resistance of persistent strains of Listeria monocytogenes and Escherichia coli.

AIMS: The aims of the project were threefold: to survey the use of disinfectants in the UK food industry; to assess the product and environmental microflora of selected food factories for the persistence of Listeria monocytogenes and Escherichia coli; and to determine the disinfectant resistance of any persistent strains. METHODS AND RESULTS: A survey of the use of disinfectants in the UK food industry was undertaken in which a total of 40 sites were visited and a further 77 postal questionnaires were returned from farms, food manufacture, food transport and food retail sites. Quaternary ammonium compounds (QACs) were predominantly used, applied in small volumes as a mist. Approximately 30,000 samples from the product and environment of five chilled food factories were examined for L. monocytogenes and E. coli over a 3 year period. A total of 181 L. monocytogenes and 176 E. coli isolates were ribotyped to yield 19 and 34 ribogroups, respectively. Some strains were isolated only from the product, a number only from the environment and others from both niches. Some strains were seen to be persistent for the duration of the sampling exercise (2-3 years). The most common L. monocytogenes and E. coli strains, together with two environmental L. monocytogenes strains, were assessed for any resistance to commercial disinfectants as compared with a laboratory L. monocytogenes disinfectant testing strain. The resistance of the L. monocytogenes and E. coli strains isolated from the factory were not significantly different from the laboratory control strain. CONCLUSIONS: Persistent strains of L. monocytogenes and E. coli are found in the UK food industry, though this persistence is not related to their increased susceptibility to the most commonly used disinfectants. SIGNIFICANCE AND IMPACT OF THE STUDY: The concept of a persistent microflora in food factories will have an impact on the future selection of suitable control options, including the use of biocides.

Biocide use in the food industry and the disinfectant resistance of persistent strains of Listeria monocytogenes and Escherichia coli.

AIMS: The aims of the project were threefold: to survey the use of disinfectants in the UK food industry; to assess the product and environmental microflora of selected food factories for the persistence of Listeria monocytogenes and Escherichia coli; and to determine the disinfectant resistance of any persistent strains. METHODS AND RESULTS: A survey of the use of disinfectants in the UK food industry was undertaken in which a total of 40 sites were visited and a further 77 postal questionnaires were returned from farms, food manufacture, food transport and food retail sites. Quaternary ammonium compounds (QACs) were predominantly used, applied in small volumes as a mist. Approximately 30,000 samples from the product and environment of five chilled food factories were examined for L. monocytogenes and E. coli over a 3 year period. A total of 181 L. monocytogenes and 176 E. coli isolates were ribotyped to yield 19 and 34 ribogroups, respectively. Some strains were isolated only from the product, a number only from the environment and others from both niches. Some strains were seen to be persistent for the duration of the sampling exercise (2-3 years). The most common L. monocytogenes and E. coli strains, together with two environmental L. monocytogenes strains, were assessed for any resistance to commercial disinfectants as compared with a laboratory L. monocytogenes disinfectant testing strain. The resistance of the L. monocytogenes and E. coli strains isolated from the factory were not significantly different from the laboratory control strain. CONCLUSIONS: Persistent strains of L. monocytogenes and E. coli are found in the UK food industry, though this persistence is not related to their increased susceptibility to the most commonly used disinfectants. SIGNIFICANCE AND IMPACT OF THE STUDY: The concept of a persistent microflora in food factories will have an impact on the future selection of suitable control options, including the use of biocides.

Impaired inhibitory G-protein function contributes to increased calcium currents in rats with diabetic neuropathy.

There is a growing body of evidence that sensory neuropathy in diabetes is associated with abnormal calcium signaling in dorsal root ganglion (DRG) neurons. Enhanced influx of calcium via multiple high-threshold calcium currents is present in sensory neurons of several models of diabetes mellitus, including the spontaneously diabetic BioBred/Worchester (BB/W) rat and the chemical streptozotocin (STZ)-induced rat. We believe that abnormal calcium signaling in diabetes has pathologic significance as elevation of calcium influx and cytosolic calcium release has been implicated in other neurodegenerative conditions characterized by neuronal dysfunction and death. Using electrophysiologic and pharmacologic techniques, the present study provides evidence that significant impairment of G-protein-coupled modulation of calcium channel function may underlie the enhanced calcium entry in diabetes. N- and P-type voltage-activated, high-threshold calcium channels in DRGs are coupled to mu opiate receptors via inhibitory G(o)-type G proteins. The responsiveness of this receptor coupled model was tested in dorsal root ganglion (DRG) neurons from spontaneously-diabetic BB/W rats, and streptozotocin-induced (STZ) diabetic rats. Intracellular dialysis with GTPgammaS decreased calcium current amplitude in diabetic BB/W DRG neurons compared with those of age-matched, nondiabetic controls, suggesting that inhibitory G-protein activity was diminished in diabetes, resulting in larger calcium currents. Facilitation of calcium current density (I(DCa)) by large-amplitude depolarizing prepulses (proposed to transiently inactivate G proteins), was significantly less effective in neurons from BB/W and STZ-induced diabetic DRGs. Facilitation was enhanced by intracellular dialysis with GTPgammaS, decreased by pertussis toxin, and abolished by GDPbetaS within 5 min. Direct measurement of GTPase activity using opiate-mediated GTPgamma[(35)S] binding, confirmed that G-protein activity was significantly diminished in STZ-induced diabetic neurons compared with age-matched nondiabetic controls. Diabetes did not alter the level of expression of mu opiate receptors and G-protein alpha subunits. These studies indicate that impaired regulation of calcium channels by G proteins is an important mechanism contributing to enhanced calcium influx in diabetes.

Treatment of aged rat sensory neurons in short-term, serum-free culture with nerve growth factor reverses the effect of aging on neurite outgrowth, calcium currents, and neuronal survival.

Impaired NGF production and release has been documented in aged animals, suggesting that decreased NGF receptor stimulation may be one factor contributing to neuronal dysfunction with aging. Other studies have suggested that aging may be associated with impaired intracellular responses to NGF. Because aging-associated neuronal dysfunction contributes to morbidity and mortality in the geriatric population, it is important to determine whether the effects of aging on sensory neuron function and survival are reversible. In the present study, we observed significantly decreased neurite outgrowth and neuronal survival in short-term cultures (0-96 h) of dorsal root ganglion (DRG) neurons from aged (>22 months) Fisher 344 x Brown Norway F1 hybrid rats, compared to young (4-6 month) and middle-aged (14 month) animals. From 24 to 96 h in culture, diminished survival of aged neurons appeared to be due to an increased rate of apoptotic cell death. DRG neurons from aged animals also exhibited significantly decreased whole cell, high-threshold voltage-dependent calcium currents, with a larger proportion of L-type current, compared to youthful and middle-aged animals. Treatment of aged DRG neurons with NGF restored neurite outgrowth, neuronal survival and calcium current amplitude and subtype distribution to those observed in youthful DRG neurons.

Effectiveness of cleaning techniques used in the food industry in terms of the removal of bacterial biofilms.

The effectiveness of cleaning was investigated through food factory trials and laboratory experiments using a naturally occurring biofilm from a food factory environment and generated biofilms. The efficacy of factory cleaning and disinfection programmes was assessed by swabbing and total viable count (TVC) analysis of surfaces before cleaning, after cleaning and after disinfection. Cleaning produced a 0.91 log reduction in the attached population. Investigation of the effectiveness of a variety of cleaning methods in the removal of a naturally occurring food factory biofilm showed that the high pressure spray and the mechanical floor scrubber, which use a high degree of mechanical action, were most effective. Cleaning trials with biofilms of Pseudomonas aeruginosa or Staphylococcus aureus showed that spraying with water at pressures of 34.5, 51.7 and 68.9 bar did not significantly increase the removal, as assessed by direct epifluorescent microscopy (DEM) and swabbing and TVC analysis, beyond the three log reduction observed at 17.2 bar. The effect of spray time at 17.2 bar showed that increasing spray time from 1 to 10 s did not significantly increase removal of Ps. aeruginosa biofilm. Investigation of the optimum distance of the spray lance from the surface at 17.2 bar was found to be between 125 and 250 mm. The use of an alkaline, acidic or neutral detergent prior to spraying with water at 17.2 bar did not significantly increase the removal of Ps. aeruginosa or Staph. aureus. However, the acidic and alkaline products significantly (P = 0.05) affected the viability of Staph. aureus and Ps. aeruginosa, respectively, thereby minimizing the potential for the spread of contamination.

kappa- and mu-Opioid inhibition of N-type calcium currents is attenuated by 4beta-phorbol 12-myristate 13-acetate and protein kinase C in rat dorsal root ganglion neurons.

In rat dorsal root ganglion neurons, activation of kappa- and mu-opioid receptors decreases N-type calcium current, whereas a constitutively active form of protein kinase C (PKC; i.e., PKM, a PKC catalytic subunit fragment) increases N-type calcium current. PKC also attenuates inhibition of calcium current by several G protein-linked neurotransmitter systems. We examined the effects of activation of endogenous PKC by 4beta-phorbol 12-myristate 13-acetate (PMA) and dialysis of cells with PKM and a pseudosubstrate inhibitor PKC(19-31) (PKC-I) on kappa- and mu-opioid-mediated inhibition of calcium current, calcium current amplitude, and rundown. PMA modestly increased peak calcium current and substantially reduced calcium current "rundown," effects blocked by PKC-I. In contrast, PKC-I decreased calcium current and increased current rundown. PMA attenuated morphine-, dynorphin A-, and U50, 488- but not pentobarbitol-related inhibition of calcium current. Similar effects were seen with intracellular dialysis of PKM. Intracellular PKC-I did not block opioid inhibition of calcium current but did reverse PMA and PKM effects on opioid receptor coupling to calcium channels. Because neither PMA nor PKM changed the proportion of omega-CgTX-inhibited current, their effects were not due to a decrease in the proportion of N-type current. After omega-CgTX treatment, there were no differences in the dynorphin A effects on control and PMA- or PKM-treated neurons, suggesting that PKC primarily affected coupling to N-type calcium channels. These data suggest that in acutely dissociated rat dorsal root ganglion neurons, endogenous PKC is required for maintenance of calcium current, may play a role in regulation of neuronal calcium channels, and could be involved in tolerance and/or cross-talk inhibition of opioid responsiveness.

Serum from patients with type 2 diabetes with neuropathy induces complement-independent, calcium-dependent apoptosis in cultured neuronal cells.

We hypothesized that sera from type 2 diabetic patients with neuropathy contains an autoimmune immunoglobulin that promotes complement-independent, calcium-dependent apoptosis in neuronal cell lines. Neuronal cells were cultured in the presence of complement-inactivated sera obtained from patients with type 2 diabetes with and without neuropathy and healthy adult control patients. Serum from diabetic patients with neuropathy was associated with a significantly greater induction of apoptosis, compared to serum from diabetic patients without neuropathy and controls. In the presence of calcium channel antagonists, induction of apoptosis was reduced by approximately 50%. Pretreatment of neuronal cells with serum from diabetic patients with neuropathy was associated with a significant increase in elevated K+-evoked cytosolic calcium concentration. Serum-induced enhancement in cytosolic calcium and calcium current density was blocked by treatment with trypsin and filtration of the serum using a 100,000-kd molecular weight filter. Treatment with an anti-human IgG antibody was associated with intense fluorescence on the surface of neuronal cells exposed to sera from patients with type 2 diabetes mellitus with neuropathy. We conclude that sera from type 2 diabetic patients with neuropathy contains an autoimmune immunoglobulin that induces complement-independent, calcium-dependent apoptosis in neuronal cells.

Serum from diabetic BB/W rats enhances calcium currents in primary sensory neurons.

We examined the hypothesis that exposure of nondiabetic rat dorsal root ganglion (DRG) neurons to sera from diabetic BB/W rats would produce an increase in calcium currents associated with impaired regulation of the inhibitory G protein-calcium channel complex. Acutely dissociated rat DRGs were incubated for 18-24 h in medium supplemented with sera (10% vol/vol) from either diabetic rats with neuropathy or age-matched, nondiabetic controls. Exposure of DRG neurons to sera from diabetic BB/W rats resulted in a surface membrane immunofluorescence pattern when treated with an anti-rat light-chain antibody that was not observed in neurons exposed to control sera. Calcium current density (IDCa) was assessed with the use of the whole cell variation of the patch-clamp technique. IDCa in neurons exposed to diabetic sera was significantly increased compared with neurons exposed to control sera. Guanine nucleotide-binding (G) protein regulation of calcium channel function was examined with the use of a two-pulse "facilitation" or IDCa enhancement protocol in the presence of activators [guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)] or antagonists [guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) and pertussis toxin (PTX)] of G protein function. Facilitation was significantly decreased in neurons exposed to diabetic sera. Intracellular diffusion of neurons with GDP beta s blocked facilitation, whereas dialysis with GTP gamma s increased facilitation to a similar magnitude in neurons exposed to either diabetic or control sera. Treatment with PTX resulted in a significant increase in IDCa and approximately 50% decrease in facilitation in neurons treated with control sera but no significant changes in neurons exposed to diabetic sera. We conclude that serum from diabetic BB/W rats with neuropathy contains an autoimmune immunoglobulin that impairs regulation of the inhibitory G protein-calcium channel complex, resulting in enhanced calcium influx. Regulation of the inhibitory G protein-calcium channel complex involves PTX-sensitive and -insensitive G proteins.

Neural injury, repair and adaptation in the GI tract. I. New insights into neuronal injury: a cautionary tale.

Understanding of the pathophysiology of neuronal injury has advanced remarkably in the last decade. This largely reflects the burgeoning application of molecular techniques to neuronal cell biology. Although there is certainly no consensus hypothesis that explains all aspects of neuronal injury, a number of interesting observations have been published. In this brief review, we examine mechanisms that appear to contribute to the pathophysiology of neuronal injury, including altered Ca2+ signaling, activation of the protease cascades coupled to apoptosis, and mitochondrial deenergization associated with release of cytochrome c, production of free radicals, and oxidative injury. Finally, evidence for neuroprotective mechanisms that may ameliorate cell injury and/or death are reviewed. Little information has been published regarding the mechanisms that mediate injury in the enteric nervous system, necessitating a focus on models outside the gastrointestinal (GI) tract, which may provide insights into enteric nervous system injury.

Failure of nimodipine to prevent or correct the long-term nerve conduction defect and increased neuronal Ca(2+)-currents in the diabetic BB/W-rat.

It has been suggested that L-type Ca2+ channel antagonists exert a beneficial effect on nerve conduction velocity (NCV) slowing in short-term experimental diabetic neuropathy. We examined the effects of long-term treatment with the L-channel blocker, nimodipine, on two aspects of neuronal function previously documented to be abnormal in the spontaneously diabetic BB/W-rat: nerve conduction velocity and calcium influx in dorsal root ganglion (DRG) neurons. Treatment with 20 mg/kg nimodipine i.p. every 48 h from onset of diabetes for 6 months led to a transient, non-significant (30%) improvement in NCV. Intervention with the same regimen from 3 to 6 months of diabetes had no corrective effect on the already established NCV defect. Voltage activated calcium currents were recorded in isolated DRG neurons from nimodipine-treated and untreated diabetic and non-diabetic age-matched BB/W control rats. The peak high-threshold calcium current density (IDCa, pA/pF) was significantly larger in non-treated diabetic rats compared with control rats (157 +/- 12 vs. 66 +/- 5.5 (P < or = 0.05)). Long-term treatment with nimodipine was associated with a non-significant (28%) decrease (112 +/- 29) in the IDCa compared with non-treated diabetic rats. We conclude that L-channel mediated perturbations of cytosolic Ca2+ levels are only of minor pathophysiologic significance in the development of chronic diabetic neuropathy.

Opiate-mediated inhibition of calcium signaling is decreased in dorsal root ganglion neurons from the diabetic BB/W rat.

The effect of diabetes mellitus on opiate-mediated inhibition of calcium current density (I(D Ca) [pA pF-1]) and cytosolic calcium response ([Ca2+]i nM) to depolarization with elevated KCl and capsaicin was assessed. Experiments were performed on isolated, acutely dissociated dorsal root ganglion (DRG) neurons from diabetic, BioBreeding/Worcester (BB/W) rats and age-matched control animals. Sciatic nerve conduction velocity was significantly decreased in diabetic animals compared to controls. Mean I(DCa) and [Ca2+]i responses to capsaicin and elevated KCl recorded in DRGs from diabetic animals were significantly larger than those recorded in DRG neurons from controls. In neurons from diabetic animals, the opiate agonist dynorphin A (Dyn A; 1, 3, and 5 microM) had significantly less inhibitory effect on I(D Ca) and KCl-induced [Ca2+]i responses compared to controls. Omega-conotoxin GVIA (omega-CgTX; 10 microM) and pertussis toxin (PTX; 250 ng ml-1) abolished Dyn A-mediated inhibition of I(DCa) and [Ca2+]i in control and diabetic neurons, suggesting that Dyn A modulated predominantly N-type calcium channels coupled to opiate receptors via PTX-sensitive (Gi/o) inhibitory G proteins. These results suggest that opiate-mediated regulation of PTX-sensitive, G protein-coupled calcium channels is diminished in diabetes and that this correlates with impaired regulation of cytosolic calcium.

Enhancement of high threshold calcium currents in rat primary afferent neurons by constitutively active protein kinase C.

Protein kinase C has been implicated in the modulation of calcium channel function. However, controversy exists concerning the actions of agents such as phorbol esters or diacylglycerol (DAG) that activate endogenous PKC, with both enhancement and inhibition of Ca2+ currents described. In this article we report the effects of direct intracellular application of a constitutively active form of PKC (PKM) on whole cell calcium currents in acutely dissociated rat dorsal root ganglion neurons. PKM application significantly enhanced high threshold voltage-activated calcium currents elicited from holding potentials of -80 mV and -40 mV. The rate of current rundown in PKM-treated cells was not significantly different from controls. The enhancement observed with PKM was not due to a shift in the voltage dependence of the peak current. Synthetic PKC inhibitor peptide (PKC-I) added to recording solutions containing PKM (PKM+PKC-I) abolished the PKM-associated enhancement. The rate of current rundown was significantly increased in the presence of PKM+PKC-I, and PKC-I alone, suggesting that substantial enhancement of voltage-activated calcium currents by endogenous PKC occurred in this preparation of rat dorsal root ganglion neurons. The portions of current attributable to N-, L-, and non-N,L-type currents [determined by applying the N- and L-type calcium antagonists omega-conotoxin GVIA and nifedipine (3-10 microM)] were not affected by PKM, suggesting that both N and L current components were enhanced by PKM.(ABSTRACT TRUNCATED AT 250 WORDS)

Voltage-dependent calcium currents are enhanced in dorsal root ganglion neurones from the Bio Bred/Worchester diabetic rat.

1. Whole-cell, high-threshold, voltage-dependent calcium currents (ICa) were enhanced in acutely dissociated, capsaicin-sensitive dorsal root ganglion neurones from diabetic Bio Bred/Worchester (BB/W) rats, compared with those from age-matched, non-diabetic controls. The magnitude of the enhancement increased with the duration of diabetes, and reached significance at diabetic durations of 6 months (diabetic: 6.3 +/- 0.4 nA; current density (CD), 157 +/- 12 pA pF-1; means +/- S.E.M., n = 9, P < 0.01; control: 3.9 +/- 0.6 nA; CD, 116 +/- 11 pA pF-1; n = 18) and 8 months (diabetic: 7.6 +/- 0.4 nA; CD, 177 +/- 25 pA pF-1; n = 11, P < 0.005; control: 5.1 +/- 0.5 nA; CD, 111 +/- 26 pA pF-1; n = 15). Low-threshold, voltage-dependent ICa were also enhanced in neurones from animals diabetic for 8 months (diabetic: 2.5 +/- 0.7 nA, n = 4, P < 0.05; control: 0.7 +/- 0.5 nA, n = 6). 2. The ICa enhancement was prevented by long-term treatment of diabetic animals with an aldose reductase inhibitor (ARI; peak ICa at 6 months: 4.41 +/- 0.48 nA, n = 2; at 8 months: 4.32 +/- 0.60 nA, n = 9). 3. The ICa enhancement was not due to a shift in the voltage dependence of either the current-voltage relationship or steady-state inactivation. 4. The L channel antagonist nifedipine and preferential N channel antagonist omega-conotoxin GVIA (omega-CgTX) caused a greater inhibition of high-threshold ICa in diabetic neurones compared with controls (nifedipine: control: 25 +/- 3%, n = 26; diabetic: 36 +/- 7%, n = 11; omega-CgTX: control: 40 +/- 4%, n = 21; diabetic: 50 +/- 7%, n = 7). Diabetic neurones also demonstrated a significantly greater residual current (2.44 +/- 0.34 nA, n = 7) in the presence of both antagonists vs. controls (1.28 +/- 0.30 nA, n = 8, P < 0.05), suggesting that N-, L- and additional non-N-, non-L-type high-threshold ICa were enhanced.

Effects of repeated subcutaneous administration of recombinant human insulin-like growth factor I in adults with growth hormone deficiency.

Insulin-like growth factor I (IGF-I) circulates bound to specific binding proteins (BPs) that modulate its effects at target cells. Hypoglycemia alters the serum levels of insulin-dependent IGFBPs and thus modifies the IGF-I action. We administered recombinant IGF-I (40 micrograms/kg body wt, from Kabi Pharmacia) in a morning dose (08.00 h) for seven consecutive days to six patients (21-47 years) with panhypopituitarism. This dose did not lead to hypoglycemia. Repeated blood sampling was performed on days 1 and 7, otherwise morning samples were drawn. The mean serum total IGF-I was maximal 3-4 h after the injection. A higher peak and basal value (p < 0.05) was observed on day 7 when compared to that observed on day 1. The concentrations were 237 vs 190 micrograms/l and 43 vs 22 micrograms/l. The mean free IGF-I increased concomitantly to 17 and 20 micrograms/l after 2-3 h on days 1 and 7. After 4 h, IGF-II was decreased (p < 0.05) from 340 to 291 micrograms/l on day 1 and from 341 to 252 micrograms/l on day 7. The IGF-I area under the curve on days 1 and 7 was correlated to the IGFBP-3 levels. Only the patient with the highest IGFBP-3 level obtained IGF-I levels above 100 micrograms/l for 24 h. In spite of unchanged glucose levels, there was a modest suppression of insulin levels (p < 0.05) between 0 and 4 h from 102 to 78 pmol/l on day 1 and from 90 to 60 pmol/l on day 7 when the subjects were fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Cecal diverticulitis mimicking appendicitis on ultrasonography.

The authors describe a case of acute cecal diverticulitis in which the ultrasonographic features, as well as the clinical features, mimicked those of acute appendicitis. Though rare, acute cecal diverticulitis is an important differential diagnosis when ultrasonographic features suggest acute appendicitis, because the condition can be managed initially without surgery.

Treatment of a calf with Clostridium chauvoei infection.

In a small beef cattle herd, two 2- to 3-month-old calves had died suddenly. A 2.5-month-old calf, with Clostridium chauvoei infection of the right hip and stifle region, was treated successfully with procaine penicillin G. The herd had not been vaccinated against any disease.