Effect of telmisartan on cholesterol levels in patients with hypertension - Saga Telmisartan Aggressive Research (STAR).

Saga Telmisartan Aggressive Research (STAR) is a single-arm, prospective multi-center trial to evaluate the effectiveness of treatment with telmisartan in patients with hypertension. A total of 197 patients with a systolic blood pressure of > or =140 or a diastolic blood pressure of > or =90 mmHg were enrolled in this study, and were prescribed 20 to 80 mg/day of telmisartan for 6 months. In all patients, both systolic and diastolic blood pressures decreased (159+/-20 to 135+/-12 mmHg, p<0.0001, 87+/-12 to 75+/-8 mmHg, p<0.0001, respectively). In addition, total cholesterol (TC) levels decreased from 200+/-40 to 188+/-33 mg/dl (p<0.05). In patients with TC > or =220 mg/dl, the change was more striking (249+/-33 to 204+/-31 mg/dl, p<0.0001). Even in patients receiving statins, TC levels still were decreased (216+/-51 to 190+/-31 mg/dl, p<0.02). In addition, TC levels were also decreased even in patients receiving telmisartan in exchange for other ARBs with TC > or =220 mg/d. Triglyceride (TG) levels were decreased (270+/-199 to 175+/-74 mg/dl, p<0.005) in patients with TG levels > or =150 mg/dl. Fasting blood glucose (FBG) was decreased (158+/-68 to 138+/-60 mg/dl, p<0.05) in patients with FBG > or =110 mg/dl. These results suggest that telmisartan may have favorable effects on lipid and glucose metabolism, in addition to lowering blood pressure. The profound effect of telmisartan to lower cholesterol suggests a potential use in hypertensive patients with dyslipidemia.

Differential control of cellular gene expression by diffusible and non-diffusible EGF.

Cell gene expression is affected by both the kind and mode of growth factor stimulation (diffusive vs. non-diffusive). Epidermal growth factor (EGF) was pattern-immobilized on a polystyrene plate. Although the growth of the rat phaeochromocytoma cell line PC12 is stimulated by diffusible EGF, and differentiation is stimulated by diffusible nerve growth factor (NGF), immobilized (non-diffusible) EGF stimulated PC12 differentiation. The immobilized EGF caused a long-lasting stimulation of the intracellular signal protein mitogen-associated protein MAP kinase (MAPK, also known as ERK) and p38 (a subfamily of the MAPK superfamily) in cells, as did diffusible NGF. The switching between growth stimulation and differentiation is considered to be due to the duration of the stimulus. The function of the biosignal conjugate was regulated using conjugation methodology.

ERK induces p35, a neuron-specific activator of Cdk5, through induction of Egr1.

The classical mitogen-activated protein kinase (MAPK; also known as extracellular-signal-regulated kinase), ERK cascade has been shown to have a crucial role in cell proliferation and differentiation. In PC12 cells, sustained activation of ERK induced by nerve-growth factor (NGF) is essential for neuronal differentiation. However, downstream targets of ERK that are essential for neuronal differentiation have not been defined. Here we show that NGF induces strong, sustained expression of p35, the neuron-specific activator of cyclin-dependent kinase 5 (Cdk5), through activation of the ERK pathway. The induced kinase activity of Cdk5 is required for NGF-induced neurite outgrowth. Our results indicate that sustained activation of ERK is necessary and sufficient for strong induction of p35. Furthermore, the transcription factor Egr1, is induced by NGF through the ERK pathway and mediates induction of p35 by ERK. Our results thus define an essential signalling pathway, downstream of ERK/MAPK, that leads to neuronal differentiation.

[Assessment of anesthesia satisfaction using direct interviews at post-anesthesia clinic].

The authors studied 5,034 consecutive patients undergoing elective surgery. Preoperative, intraoperative, and postoperative variables were gathered and patient satisfaction was assessed using direct interviews at pre- and post-anesthesia clinic. Fifty-nine percent of the 4,717 responders showed satisfaction and 4% showed dissatisfaction with anesthesia. The most undesirable perioperative outcome was vomiting/nausea. Other undesirable outcomes include discomfort of urine catheter, sore throat, memory of extubation, postoperative pain and so on. Anesthesiologist can improve the quality of anesthesia by preoperative explanation and preventative management for undesirable perioperative outcomes.

Measurement of the back fat layer in beagles for estimation of obesity using two-dimensional ultrasonography.

The purpose of this study was to select a suitable location for measuring the subcutaneous fat layer in beagles as an indicator of excess body fat deposition. A location suitable for such a measurement should meet five conditions--it should be easy to: (1) apply the probe, (2) detect the anatomical character of the measurement location, and (3) obtain a reproducible ultrasonogram at all times. In addition, the fat layer should be (4) thick enough for measuring, and (5) located in an area that varies markedly with the degree of obesity. Ultrasonograms made in the transverse planes on the top of the spinous process of the sixth lumbar vertebra, the seventh lumbar vertebra and the first sacral vertebra were found to be suitable for measurement. The depth and area of the back fat layer at these locations were closely related to the degree of obesity.

[Effect of colforsin daropate hydrochloride after cardiopulmonary bypass].

We evaluated the effects of colforsin daropate hydrochloride (CDH) after cardiopulmonary bypass (CPB) in comparison with milrinone. CDH or milrinone were given during and after CPB combined with cathecholamines so as to maintain mean arterial pressure (mABP > 60 mmHg) and cardiac index (CI > 3.0 l.min-1.m-2). Hemodynamics measurement was done immediately after CPB (A 1), one hour after CPB (A 2) and after the chest closure (A 3). In CDH group, mABP was significantly higher compared with milrinone group. Also, CDH group showed a significant reduction in the cases of combined use of dobutamine (at A 2, A 3) and norepinephrine (at A 1, A 2) compared with milrinone group. In conclusion, colforsin daropate hydrochloride exerts more inotropic effect and could reduce the necessity of combined use of cathecholamine compared with milrinone.

Quantitative single photon emission tomography analysis for the diagnosis of transient global amnesia: adaptation of statistical parametric mapping.

We report two cases of transient global amnesia (TGA) diagnosed using a clinical criteria and single photon emission tomography (SPECT) with the aid of Statistical Parametric Mapping (SPM). Both patients underwent an initial SPECT study about 20 h after the disappearance of the amnesic episode, and a second study 3 weeks after the episode. We conducted quantitative cerebral blood flow (CBF) analyses using SPM on Matlab. This revealed regions with abnormal CBF in the first studies but not in the second. This method appears to be useful for diagnosis of TGA, especially in patients with suspected TGA in whom the amnesic episode disappears within a few days.

Mental stress test is an effective inducer of vasospastic angina pectoris: comparison with cold pressor, hyperventilation and master two-step exercise test.

BACKGROUND: Cold pressor, hyperventilation and exercise stress tests were usually used for inducing an angina attack in patients with vasospastic angina pectoris. We induced vasospastic angina attack using the mental calculation stress test, and compared the results with those using other stress tests. SUBJECTS AND METHODS: Subjects were 29 patients with vasospastic angina pectoris. Their ages were 60.8+/-8.4 years. Coronary vasospasm was induced by an acetylcholine infusion test during coronary angiography. The mental stress test was performed as follows; after memorizing six digits numbers, they repeated these numbers in reverse for 5 min, and performed serial subtraction of 17 from 1000 for 5 min. Blood pressure, heart rate and ECG were recorded every 1-5 min during the mental stress test. The serum concentrations of epinephrine and norepinephrine were measured before and during the mental stress test. We compared these results with those obtained using cold pressor, hyperventilation and the Master two-step exercise stress test. RESULTS: (1) Eight of the 29 patients (28%) showed ischemic ST-T change, which was caused by the mental stress test. (2) The increase in norepinephrine was greater in patients with an ST-T change than without an ST-T change (0.11+/-0.06 vs. 0.04+/-0.04 ng/ml, P<0.01). (3) The incidence of the ST-T change caused by the mental stress test (28%) was similar to the cold pressor test (27%) and greater than that caused by the hyperventilation test (13%). The incidence of ST-T change caused by the Master two-step test was 55%. CONCLUSIONS: The mental stress test is an effective inducer of vasospastic angina attack, and attack may be induced by neurohumoral vasoconstrictive reflex and/or increased left ventricular afterload.

Requirement for mitogen-activated protein kinase in cerebellar long term depression.

The mitogen-activated protein kinase (MAPK) cascade has been shown to play an essential role in regulation of cell proliferation and cell differentiation. Although mammalian MAPKs are most abundantly expressed in postmitotic and terminally differentiated neuronal cells, their function in the central nervous system is still largely undefined. We present evidence here for a role of the MAPK cascade in cerebellar long term depression (LTD), which is a widely studied form of synaptic plasticity in mammalian brain. In cultured Purkinje cells, LTD is known to be induced by iontophoretic application of glutamate and depolarization of Purkinje cells. We found that MAPK was activated in Purkinje cells by treatment of primary cultures of rat embryonic cerebella with glutamate and a depolarization-inducing agent, KCl. Application of PD98059, a specific inhibitor of MAPK kinase (MAPKK/MEK), inhibited both the activation of MAPK and the induction of LTD in Purkinje cells. Furthermore, the induction of LTD was completely blocked by introduction into Purkinje cells of anti-active MAPK antibody, which was found to specifically and potently inhibit the activity of MAPK. These results suggest that postsynaptic activation of the MAPK cascade is essential for the induction of cerebellar LTD.

[A case of encephalitis due to Mycoplasma pneumoniae: detection of specific DNA from cerebrospinal fluid and elevation of interleukin-6].

A 9-year-old female was admitted to our hospital due to a generalized seizure and consciousness disturbance. The patient had a fever and rash four days before admission, but she had no respiratory symptoms. The seizure and consciousness disturbance was prolonged and intractable. We diagnosed the patient as having encephalitis because of the increase in the cell count in the cerebrospinal fluid (CSF) and a diffuse slow EEG wave. The computed tomography of the head was normal. The causative agent was identified as Mycoplasma pneumoniae because of the increase of antibodies, and the detection of a specific DNA with a polymerase chain reaction. The interleukin (IL)-6 level of CSF was high (384 pg/ml). In spite of intensive treatment she had severe neurological sequelae. The invasion of Mycoplasma pneumoniae to the central nervous system appeared to have a role in the development of encephalitis in the patient. We speculated that there is a possible relationship between the IL-6 levels of CSF and clinical severity of encephalitis.

Requirement of p38 mitogen-activated protein kinase for neuronal differentiation in PC12 cells.

Nerve growth factor (NGF) induces sustained activation of classical MAP kinase (MAPK, also known as ERK) and neuronal differentiation in PC12 cells, whereas epidermal growth factor (EGF) induces transient activation of ERK/MAPK and stimulates proliferation of the cells. Although previous studies showed that sustained activation of ERK/MAPK is important for neuronal differentiation of the cells, a recent report revealed that inhibition of the sustained phase of ERK/MAPK activation alone does not block neurite outgrowth caused by NGF. These results suggest requirement for an additional signaling pathway(s) triggered by NGF in neuronal differentiation. Here we show that NGF induces sustained activation of p38, a subfamily member of the MAPK superfamily, and that inhibition of the p38 pathway blocks neurite outgrowth in PC12 cells. Surprisingly, expression of constitutively active MAPK/ERK kinase (MAPKK, also known as MEK) results in p38 activation as well as ERK/MAPK activation, and a p38 inhibitor blocks neurite outgrowth caused by the constitutively active MAPKK/MEK. Moreover, constitutive activation of p38 is able to induce neurite outgrowth when combined with EGF treatment. These results reveal an essential role of p38 in neuronal differentiation in PC12 cells.

[A study for serodiagnosis of verotoxin-producing Escherichia coli (enterohemorrhagic E. coli) O157 by the bacterial agglutination technique].

We evaluated the usefulness of bacterial agglutination antibodies for serodiagnosis of verotoxin-producing Escherichia coli (enterohemorrhagic E. coli) O157 infections. We examined 50 serum samples from 50 control children (whiout diarrhea 31, with diarrhea 19), 24 samples from 8 diarrhea cases due to O157:H7, 37 samples from 14 cases of hemolytic uremic syndrome (HUS) for antibodies to heat-killed E. coli E32511 (O157:H.-) strain using the bacterial agglutination technique. Of the control sera all but one (x80) showed 20 > or = in the antibody. All the diarrhea patients due to O157:H7 showed a significant rise (x160-x5120) of the titers in the sera at 5-7 days on illness, after that the titers fell rapidly. Significant antibody rise (x160-x5120) was detected in twelve out of 14 HUS patients at the early stage of the illness which fell in the convalescent phase. The assay appeared to be a useful serodiagnostic technique because of its easiness and simplicity as well as because of its high sensitivity and specificity.

Activation and involvement of p38 mitogen-activated protein kinase in glutamate-induced apoptosis in rat cerebellar granule cells.

In the mammalian central nervous system glutamate is the major excitatory neurotransmitter and plays a crucial role in plasticity and toxicity of certain neural cells. We found that glutamate stimulated activation of p38 and stress-activated protein kinase (SAPK, also known as c-Jun N-terminal kinase (JNK)), two subgroup members of the mitogen-activated protein kinase superfamily in matured cerebellar granule cells. The p38 activation was largely mediated by N-methyl-D-aspartate receptors. Furthermore, we have revealed a novel signaling pathway, that is, Ca2+-mediated activation of p38 in glutamate-treated granule cells. The glutamate concentration effective for inducing apoptosis correlated with that for inducing p38 activation. SB203580, a specific inhibitor for p38, inhibited glutamate-induced apoptosis. Thus p38 might be involved in glutamate-induced apoptosis in cerebellar granule cells.

[Analysis of verotoxin-producing Escherichia coli (O157:H7) strains isolated in the Fukuoka area in 1994 by pulsed-field gel electrophoresis].

Nine verotoxin-producing Escherichia coli O157:H7 strains were isolated from 9 pediatric patients with sporadic enteritis between July and September 1994 at four clinics in the Fukuoka area. The patients included two families with two cases each. These strains were analyzed by pulsed-field gel electrophoresis for Xba I-digested DNA fragments. The restriction patterns were identical between each two strains within the two family outbreaks, but different among the seven strains of the distinct seven sporadic cases. It is strongly suggested that the seven sporadic cases were infected through distinct sources, and that the two family cases were due to a common source of infection or person to person infection.

Epidemiologic application of pulsed-field gel electrophoresis to an outbreak of Campylobacter fetus meningitis in a neonatal intensive care unit.

An outbreak of nosocomial Campylobacter fetus meningitis occurred in a neonatal intensive care unit (NICU). Eight C. fetus strains were isolated from 4 infants with meningitis, the mother of the index patient and 2 infants who were asymptomatic intestinal carriers. The pulsed-field gel electrophoresis (PFGE) pattern with the restriction endonucleases Smal and Sall were found to be identical for the nosocomial C. fetus isolates, but the patterns were different from those of sporadic strains. These nosocomial strains were strongly suspected to be a single strain. The finding revealed that the index patient was infected by the mother, and that the outbreak developed from this patient by cross-infection. This is the first confirmed nosocomial C. fetus meningitis outbreak spread by cross-infection in a NICU.

Southern blotting analyses of strains of Campylobacter fetus using the conserved region of sapA.

Chromosomal DNA of 27 strains of Campylobacter fetus was analyzed by Southern blotting with a probe of the conserved region of sapA. The probe hybridized with 23 strains that produced type A lipopolysaccharide. These strains had more than six sapA homologs. In Southern blots of SalI-digested chromosomal DNA separated by pulsed-field gel electrophoresis, one fragment from 19 strains and two fragments from 4 strains hybridized. These data indicate that multiple sapA homologs are localized to a limited region on the chromosomal DNA of C. fetus and thus suggest the possibility of developing a typing system using this method.

Indirect hemagglutination assay for antibodies to Escherichia coli lipopolysaccharides O157, O111 and O26 in patients with hemolytic uremic syndrome.

We examined sera from 10 patients with hemolytic uremic syndrome (HUS) and 51 controls, with and without diarrhea, for antibodies to Escherichia coli lipopolysaccharides (LPS) O157, O111 and O26 using the indirect hemagglutination (IHA) assay. A significant rise (to a titer of > or = 2560) in IHA antibody to O157 LPS was detected in eight of the 10 HUS patients, to O111 in two patients, one of whom showed concomitantly an antibody rise to O157, but to O26 in no patients. The IHA titers fell rapidly after the acute phase of the illness. Of the control sera 15 (29.4%) non-specifically agglutinated uncoated sheep red blood cells (SRBC) at a titer of > or = 80, six (3.9%) at > or = 320 and the maximum was 640. In spite of the relatively low level of non-specific agglutination the IHA appeared to be a useful screening method to identify verotoxin-producing E. coli infections at the early stage of HUS because the titers were clearly higher than non-specific agglutination and the assay is easy to perform and gives results quickly. Artificial carriers are being considered for use in place of SRBC to diminish the non-specific hemagglutination.

[Isolation of verotoxin-producing Escherichia coli from pediatric patients suffering from enteritis with bloody stool and intussusception].

We tried to isolate verotoxin-producing Escherichia coli (VTEC) on sorbitol-MacConkey (SMAC) agar and in part by the polymerase chain reaction (PCR) method from sporadic enteritis patients with bloody stools and intussusception patients who came to three pediatric clinics in the Fukuoka area from October 1990 to September 1994. VTEC O157:H7 strains were isolated from 6 (10.5%) of 57 patients with bloody stools, Campylobacter spp. 15 (26.3%), Salmonella spp. 14 (24.6%) and Yersinia enterocolitica 2. We were not able to detect VT genes by PCR from 11 of 20 patients from whose stools no causative bacteria were isolated. Massive fresh bloody stools following frequent watery diarrhea were typical of the VTEC enteritis patients. Only 1 patient had fever and 2 had leukocytosis, but the C-reactive protein in all of them was below 1+. The VTEC strains were isolated during the summer season, 1 in June, 2 in July, and 3 in September. Since in the area O157:H7 appeared to be the most prevalent VTEC serotype, SMAC is very useful for screening VTEC in bloody stools. VTEC seems to be a rare pathogen of intussusception because the organisms were detected from none of the 30 patients.