Addition of low-dose liraglutide to insulin therapy is useful for glycaemic control during the peri-operative period: effect of glucagon-like peptide-1 receptor agonist therapy on glycaemic control in patients undergoing cardiac surgery (GLOLIA study).

AIM: To test the hypothesis that the addition of a glucagon-like peptide-1 receptor agonist that can decrease glucose levels without increasing the hypoglycaemia risk will achieve appropriate glycaemic control during the peri-operative period. METHODS: We studied 70 people with Type 2 diabetes who underwent elective cardiac surgery. Participants were randomized to either an insulin-alone or an insulin plus liraglutide 0.6 mg/day group. We evaluated average M values, which indicated the proximity index of the target glucose level from day 1 to day 10. RESULTS: The average M value in the liraglutide plus insulin group was significantly lower than that in the insulin-alone group (liraglutide plus insulin 5.8 vs insulin-alone 12.3; P < 0.001). The frequency of insulin dose modification in the liraglutide plus insulin group was significantly lower than that in the insulin-alone group (odds ratio 0.19, 95% CI 0.08-0.49; P < 0.001). The frequency of hypoglycaemia in the liraglutide plus insulin group tended to be lower than that in the insulin-alone group (odds ratio 0.57, 95% CI 0.15-2.23; P = 0.21). CONCLUSIONS: The results of this study showed that the addition of low-dose liraglutide to insulin achieved lower M values than insulin alone, suggesting that the addition of low-dose liraglutide may achieve better glycaemic control during the peri-operative period. (Clinical trials registry no.: UMIN 000008003).

Gene yerP, involved in surfactin self-resistance in Bacillus subtilis.

Surfactin is a cyclic lipopeptide biosurfactant. Transposon mutagenesis was performed in Bacillus subtilis strain 168, and a surfactin-susceptible mutant, strain 801, was isolated. Analysis of the region of insertion revealed that yerP was the determinant of surfactin self-resistance. YerP had homology with the resistance, nodulation, and cell division (RND) family proton motive force-dependent efflux pumps only characterized in gram-negative strains. The yerP-deficient strain 802, in which the internal region of the yerP gene of B. subtilis strain 168 was deleted, showed susceptibility to acriflavine and ethidium bromide. When strain 802 was converted to a surfactin producer by introducing a functional sfp which encodes a 4'-phosphopantetheinyl transferase and is mutated in B. subtilis strain 168, this yerP-deficient strain produced surfactin, although surfactin production was significantly reduced. The expression of yerP was at its maximum at the end of the logarithmic growth phase and was not induced by surfactin. yerP is the first RND-like gene characterized in gram-positive strains and is supposed to be involved in the efflux of surfactin.

Menstrual cycle-specific inhibition of endometrial stromal cell proliferation by oncostatin M.

We have investigated the possible roles of oncostatin M (OSM), which is a member of the interleukin-6 family of cytokines, in endometrial and endometriotic stromal cell growth. Endometrial and endometriotic stromal cells were collected from the uterus or ovarian chocolate cysts. We observed the expression of mRNA transcripts for OSM, OSM receptor subunit beta, leukaemia inhibitory factor receptor subunit (LIFR), and glycoprotein 130 in endometrial and endometriotic stromal cells. We also examined the effects of OSM (0-50 ng/ml) and LIF (0-10 ng/ml) on endometrial and endometriotic stromal cell proliferation and evaluated the effects of OSM on endometrial stromal cell differentiation. The presence of 10-50 ng/ml OSM significantly suppressed endometrial stromal cell growth in secretory phase tissue but not in proliferative phase tissue. In contrast, stromal cells in endometriotic tissues were resistant to the inhibitory effects of OSM. Addition of LIF did not influence the growth of endometrial stromal cells. We also showed that 10 ng/ml OSM stimulated markers of differentiation causing increased prolactin secretion and cyclooxygenase-2 gene expression in endometrial stromal cells from the secretory phase. These results suggest that OSM may play a pivotal role in regulating the growth and differentiation of endometrial cells. Endometriotic cells may behave differently from normal endometrial cells in terms of the inhibitory response to OSM.

Coasting may reduce the severity of the ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome.

The aim of our study was to determine the efficacy of postponing administration of human chorionic gonadotropin while continuing daily gonadotropin-releasing hormone agonist therapy ('coasting') to prevent the occurrence of severe ovarian hyperstimulation syndrome (OHSS) for patients with polycystic ovary (PCO) syndrome. Five patients with PCO who had been hospitalized due to severe OHSS in previous in vitro fertilization and embryo transfer or intrauterine insemination cycles at the Tottori University Hospital were included in the study. The rates of mature oocytes and fertilization were comparable between the cycles. A singleton pregnancy was achieved in a patient during the coasting cycle, and none of the women developed severe OHSS in coasting cycles. The results suggest that coasting may be an alternative method for reducing the severity of OHSS in patients with PCO.

Suppressing effects of short-chain fatty acids on growth hormone (GH)-releasing hormone-induced GH release in isolated anterior pituitary cells of goats.

The involvement of tetrodotoxin-sensitive Na+ channels and receptor-operated nonspecific Ca2+ channels, and the effects of short-chain fatty acids, on growth hormone (GH) release induced by GH-releasing hormone (GHRH) were investigated in cultured and freshly isolated caprine anterior pituitary cells. In 3-d cultured cells in Dulbecco's modified Eagle's medium, an increase in GH release induced by GHRH (10 nmol/l) was moderately, but significantly, reduced by a voltage-sensitive Na+ channel antagonist tetrodotoxin (1 micromol). The GHRH-induced GH increase, which was not affected by a simultaneous addition of a receptor-operated nonspecific Ca2+ channel antagonist tetramethrine (0.1 mmol/l), was significantly reduced by a voltage-sensitive L-type Ca2+ channel antagonist nifedipine (1 micromol/l). Propionate and butyrate at 10 mmol/l, however, not only suppressed basal GH release but also significantly reduced the GH increase induced by 10 nmol/l of GHRH. The inhibitory action of these acids was also reproduced by an addition of beta-hydroxy butyrate (10 mmol/l) and octanoate (10 mmol/l). In freshly isolated and perifused cells, butyrate (10 mmol/l) as well as somatostatin (100 nmol/l) significantly reduced the GH increase induced by GHRH. From these findings we conclude that tetrodotoxin-sensitive Na+ channels and voltage-dependent L-type Ca2+ channels are involved in the cellular mechanism for GHRH-induced GH release, and that short-chain fatty acids such as propionate and butyrate have a direct action on somatotrophs to reduce basal and GHRH-induced GH release, in caprine somatotrophs.

[The usefulness of dynamic computed tomography scanning in predicting the outcome of acute stroke patients].

The aim of this study was to investigate whether brain dynamic computed tomography (CT) is useful in predicting clinical outcome. Thirty patients suffering from cerebral ischemia in the territory of the middle cerebral artery (MCA) underwent dynamic CT scanning within 6 hours of stroke onset. Regions of interest (ROIs) were placed in the bilateral MCA territories and three parameters, peak value (PV), time to peak (TP), and PV divided by TP, were calculated from time-density curves (TDCs) on ROIs. After conventional treatment using pharmacological agents, the 30-day clinical outcome was evaluated on the Glasgow outcome scale. To investigate the relationship between the disease-to-contralateral side ratio of each parameter's value and 30-day clinical outcome, TDCs were classified into the following four types; type 1, with TP ratio less than 1.1; type 2, with TP ratio ranging from 1.1 to 1.5 and PV/TP ratio more than 0.75; type 3, with TP ratio ranging from 1.1 to 1.5 and PV/TP ratio less than 0.75; and type 4, with TP ratio more than 1.5 and PV/TP ratio less than 0.3. Clinical outcome in patients with type 1 or 2 TDC was better than in patients with type 3 or 4 TDC (p < 0.01, Fisher's exact test). We can conclude that dynamic CT is a useful means for estimating the clinical prognosis of acute stroke patients after conventional treatment. Poor clinical outcome following conventional therapy is expected in patients with type 3 or 4 TDC in contrast to patients with type 1 or 2 TDC.

Growth hormone release induced by an amino acid mixture from primary cultured anterior pituitary cells of goats.

The effects of amino acids on growth hormone (GH) release and cytosolic calcium concentration ([Ca2+]i) were investigated in caprine anterior pituitary cells cultured for 3 d in Dulbecco modified Eagle medium. The addition of an amino acid mixture consisting of seven nonessential amino acids (NEAA: L-Asp, Gly, L-Ala, L-Ser, L-Pro, L-Asn, and L-Glu; concentration of each 12.5-200 mumol/l) in the medium significantly raised GH release from the cultured cells in a concentration-dependent manner with the maximum release at 200 mumol/l NEAA. Although an addition of L-Asp (0.1-100 mumol/l) caused a significant rise in GH release in a concentration-dependent manner, neither the individual amino acids contained in NEAA except L-Asp nor others (L-Leu, L-Phe, L-Gln, L-Met, and L-Arg) caused a rise in GH release when added alone to the medium. The rise in GH release induced by NEAA (200 mumol/l) and GH-releasing hormone (GHRH, 10 nmol/l) was significantly reduced by the addition of EGTA (1.8 mmol/l) and nifedipine (1 mumol/l) to the medium, respectively. The addition of NEAA (200 mumol/l) caused a rapid and transient [Ca2+]i increase, followed thereafter by a steady increase. The prior addition of nifedipine (1 mumol/l), which itself significantly reduced the basal [Ca2+]i, completely abolished the response induced by NEAA or GHRH. From these findings, we conclude that: 1) NEAA raises GH release and [Ca2+]i in cultured caprine anterior pituitary cells, and 2) Ca2+ influx from the medium may be responsible for the cellular action of NEAA.

Anti-HTLV-1 antibody positive cutaneous T-cell lymphoma.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a neoplasm of the mature helper T-lymphocyte. Human T-lymphotropic virus type 1 (HTLV-1) has been shown to be the cause of this neoplasm. Recently, however, the HTLV-1 genome has been found in some patients with cutaneous T-cell lymphoma (CTCL), which suggests a causal relation of HTLV-1 to CTCL. Thus, the relation between the HTLV-1 genome and CTCL, as well as the difference between ATLL and CTCL, have come into question. METHODS: The authors examined two patients with CTCL whose serum anti-HTLV-1 antibodies were constantly positive. The Southern blot technique, inverse polymerase chain reaction (IPCR), and polymerase chain reaction (PCR) with four sets of primers for gag, pol, env, and pX regions of HTLV-1 were used to clarify the distinctions between ATLL and CTCL. RESULTS: Clinically, one patient presented with multiple subcutaneous nodules with involvements of the internal organ, and the other patient was typical for mycosis fungoides. No integration of HTLV-1 DNA was detected by IPCR or the Southern blot technique in either patient. PCRs with the four sets of primers were all found to be positive for HTLV-1 except one. CONCLUSIONS: The authors conclude that ATLL should be differentiated from CTCL in view of the responsibility of HTLV-1 for promoting or maintaining CTCL.

Churg-Strauss syndrome: report of a case without preexisting asthma.

A 38-year-old male with no history of asthma, who initially presented with episcleritis and subsequently developed symptoms of systemic vasculitis with marked blood eosinophilia, was diagnosed as having Churg-Strauss syndrome (CSS). Both the patient's skin lesions and pulmonary infiltrates revealed histologically proven vasculitis with predominantly eosinophilic infiltration. All the symptoms of systemic vasculitis except the persisting peripheral neuropathy dramatically improved after corticosteroid was systemically used. Since scattered non-asthmatic cases of CSS have been reported recently, and three such patients have died of acute heart failure due to delayed diagnosis, absence of asthma should not be regarded as an absolute criterion for exclusion of the diagnosis of CSS. Earlier recognition of this disease is important, since earlier institution of steroid therapy can prevent the acute onset of fatal cardiac involvement during the course of this disease.