Suppression of the nocturnal free fatty acid levels by bedtime cornstarch in NIDDM subjects

The aim of the present study was to examine the effects of a large dose of slow-release carbohydrates (CHOs) at bedtime on the nocturnal glucose, insulin and free fatty acid (FFA) levels, and to assess the putative effects on morning fasting and post-prandial glucose levels in patients with moderately controlled non-insulin-dependent diabetes mellitus (NIDDM). Unheated cornstarch (106 g of CHO) or a mixed equicaloric meal (58 g of CHO) was given at 22.00 hours to 10 NIDDM patients. For comparison, the patients were also given a smaller mixed meal at 22.00 hours on a third occasion (17 g of CHO). Compared with the mixed meals, cornstarch led to a slightly elevated early-morning plasma insulin level and a suppression of the nocturnal FFA level ( P  < 0.05), as well as to a reduced incremental glucose level (IAUC) after breakfast the next morning by approximately 30% ( P  < 0.05). There was a significant and linear relationship between the nocturnal FFA level and the glucose IAUC after breakfast ( r  = 0.44, P  < 0.02), indicating that the effect may have been mediated by the suppressive effect of cornstarch on nocturnal lipolysis. In summary, bedtime intake of unheated cornstarch in NIDDM subjects is associated with a suppression of the nocturnal FFA levels and a reduced glucose IAUC after breakfast. As the treatment did not improve overall glucose control, studies of the effects of an individually titrated amount of cornstarch are proposed to further explore the putative favourable effects of bedtime cornstarch in the treatment of NIDDM.     

Recessive epidermolysis bullosa simplex associated with plectin mutations: infantile respiratory complications in two unrelated cases

Plectin is a 500kDa protein involved in cytoskeleton-plasma membrane attachment with a wide tissue distribution including cutaneous and airway epithelia, muscle and neuronal tissue. Recently, mutations in the gene encoding plectin (PLECI) have been implicated in the pathogenesis of an autosomal recessive variant of epidermolysis bullosa simplex in which cutaneous blistering starting in the neonatal period is associated with muscular dystrophy in later life. In this study, we report two unrelated patients, both of consanguineous parentage, who presented with cutaneous blistering and a hoarse cry from birth. Both experienced inspiratory stridor and respiratory distress, necessitating emergency tracheostomy in one case. Immunoreactivity to monoclonal antibodies against plectin was absent or markedly reduced in skin biopsies from both patients. Electron microscopy revealed a low intraepidermal plane of cleavage and hypoplastic hemidesmosomes with a reduced association with keratin intermediate filaments. Direct sequencing of PLEC1 in each case demonstrated two novel homozygous frameshift deletion mutations. 5069del19 and 5905del2, which both create downstream premature termination codons. Although currently neither patient has symptoms of muscle disease, the identification of mutations in PLEC1 may be predictive for the future development of muscular dystrophy. Recessive epidermolysis bullosa simplex resulting form abnormalities in plectin should be considered in the differential diagnosis of cutaneous blistering, hoarseness and stridor in infancy.     

Urinary Enzymes and Protein Patterns as Indicators of Injury to Different Regions of the Kidney

Urinary Enzymes and Protein Patterns as Indicators of Injuryto Different Regions of the Kidney. STONARD, M. D., GORE, C.W., OLIVER, G. J. A., AND SMITH, I. K. (1987). Fundam. Appl.Toxicol. 9, 339–351. Acute experimental models of renaldamage to the proximal tubular, glomerular, and papillary regionsof the rat were produced by administration of hexachloro 1:3-butadiene(HCBD), puromycin aminonucleoside (PAN), and 2-bromoethylamine(BEA), respectively. Several routine indicators of nephrotoxicity,the enzymes alkaline phosphatase and N-acetyl-ß-glucosaminidase,and the molecular weight pattern of protein excretion were determinedon urine samples. Tubular damage produced by HCBD or BEA wasdiscriminated both quantitatively and qualitatively from glomerulardamage produced by PAN. The latter was characterized by a pronouncedincrease in protein excretion, especially proteins with molecularweight >40,000 Da. In contrast, protein excretion in tubulardamage was raised only slightly and characterized by excretionof proteins of a wide range of molecular weights. Proximal tubulardamage caused by HCBD and papillary damage caused by BEA weredistinguished both by conventional urinalysis (volume and specificgravity) and by measurement of the two urinary enzymes. Alkalinephosphatase and glucose were markedly and transiently elevatedin proximal tubular damage and N-acetyl-ß-glucosaminidaseshowed a sustained elevation in papillary damage. It is concludedthat both selective urinary enzymes and the molecular weightpattern of urinary proteins can be used to provide diagnosticinformation about the possible site of renal damage.     

Comparative vaccination of cattle against Boophilus microplus with recombinant antigen Bm86 alone or in combination with recombinant Bm91

Cattle were vaccinated either with a single recombinant tick antigen, Bm86 or with a combination of two recombinant antigens, Bm86 and Bm91 from the tick Boophilus microplus . In three experiments, the responses of cattle to subsequent challenge with the tick were assessed. The addition of the Bm91 antigen enhanced the efficacy of the vaccination over that with Bm86 alone to a statistically significant degree. Moreover, co-vaccination with two antigens did not impair the response of cattle to the Bm86 antigen. Finally, responses of individual cattle to the two antigens were independent. All of these results may be relevant to the increase in efficacy expected from a dual antigen vaccine.     

Subcutaneously administered recombinant human β-interferon in the treatment of chronic hepatitis B virus infection

Background: Treatment of chronic replicative hepatitis B virus (HBV) infection is aimed at stopping viral replication and preventing the development of chronic liver disease. β-Interferon treatment has been less well studied than α-interferon. Methods: The efficacy and tolerability of a 6-month course of subcutaneously administered human recombinant β-interferon (rINF-β_ser) was studied and the results of a low-dose regime compared with a high-dose regime. Twenty patients (17 men and three women), aged 24–54 years, with chronic hepatitis B virus infection (all hepatitis B surface antigen-positive with detectable HBV-DNA in their sera for at least 3 months prior to therapy) were randomized into two treatment groups of 10 patients each. The low-dose group received 6×10⁶ U/dose and the high-dose group received 30×10⁶ U/dose, both groups receiving their respective doses three times a week initially for 1 month and continuing for a total of 6 months. Results: The treatment was well tolerated in both groups. None of the patients required dosage reduction or cessation of treatment because of side-effects. HBV-DNA decreased in all patients during treatment, demonstrating the anti-viral efficacy of rINF-β_ser, and was undetectable in 20 and 40% of patients receiving low-dose and high-dose regimes, respectively, at the end of 6 months treatment (P=N.S.). One year after completion of treatment, HBV-DNA was undetectable in 50 and 30% of patients in the low-dose and high-dose groups, respectively (P=N.S.). However, only one patient achieved seroconversion with loss of the hepatitis B surface antigen and appearance of an anti-hepatitis B ‘e’ antigen at the end of 18 months. Conclusion: This study shows that subcutaneously administered rINF-β_ser is well tolerated, but the optimal dose and duration of treatment still needs to be defined by further studies.     

Relationship of actin filament assembly to clearance of fibrinogen gold, GPIIb-IIIa complexes on spread platelets

Abstract. The present study has evaluated the influence of high concentrations of cytochalasins B and E on the detergent-resistant actin levels in fully spread platelets by PAGE gel electrophoresis, and the effects of the two inhibitors of new actin filament assembly on translocation of fibrinogen gold (Fgn/Au) labelled GPIIb-IIIa receptors on the surface-activated cells. Concentrations of 10^{- 4}m and 10^-5 m cytochalasin B and E reduced detergent-resistant actin in fully spread platelets to levels present in resting discoid platelets in suspension. Despite reduction of actin filaments to levels in resting cells, cytochalasin B did not prevent translocation of Fgn/Au from platelet margins into channels of the open canalicular system (OCS). Similar concentrations of cytochalasin E completely blocked translocation of receptor-ligand complexes and produced a patching phenomenon not observed in previous studies. Rinsing of the spread cells to remove cytochalasin, followed by incubation of the treated platelets in Hank's buffered salt solution (HBSS) restored levels of detergent-resistant actin to those found in untreated, spread platelets. Resting grids of 10 ⁵ m cytochalasin E-treated platelets on drops of HBSS for 15min restored their ability to clear FGN/Au linked to GPIIb-IIIa from exposed surfaces to the OCS, but 10^-4 m cytochalasin E-treated cells remained anergic after incubation on drops of HBSS. Thus a fully assembled cytoplasmic actin filament cytoskeleton does not appear to be essential for translocating receptor-ligand complexes on the platelet surface to the OCS, nor does its presence guarantee that the ability to clear GPIIb-IIIa receptors will be restored.     

LOCAL RADIOTHERAPY FOR PEDAL MANIFESTATIONS OF HLA-B27-RELATED ARTHROPATHY

Four males with characteristic foot manifestations of HLA-B27-relatedarthropathy are reported. The severity of this problem and itsrecalcitrance to standard therapies led to the use of localradiotherapy. The beneficial outcome and minimal short-termside effects of this treatment are discussed in relation toprevious experience with radiotherapy in ankylosing spondylitis. KEY WORDS: HLA-B27, Radiotherapy, Spondyloarthropathy, Enthesopathy     

THE IMPACT OF ALCOHOL ON THE ACUTE HOSPITAL SERVICE: PATIENT PRESENTATION, ADMISSION AND THE PERCEPTION OF ALCOHOL USE IN SUCH GROUPS

Patients presenting to an Emergency Department were assessedby a standard questionnaire and clinical examination as to thecontribution that alcohol made to their presentation and theperception of their alcohol use. Patients under the influenceof alcohol are more than twice as likely not to fill in simplequestionnaires and not to perceive their alcohol consumptionas different from non-drinking fellows. Emergency Departmentsare not the optimal site for the education and motivation ofdrinking patients to alter their future habits.