RETRACTED ARTICLE: Effects of dobutamine on the fatigued diaphragm: A comparison with dopamine

We examined the effects of dopamine (DOA) 10 μg·kg⁻¹·min⁻¹ I.V. and dobutamine (DOB) 10 μg·kg⁻¹. min⁻¹ I.V. on the contractility of the fatigued diaphragm in 26 anesthetized, mechanically ventilated dogs. Animals were divided into two groups of 13 each: the DOA and DOB groups. Diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Diaphragmatic contractility was assessed from changes in transdiaphragmatic pressure (P_di). After diaphragmatic fatigue, P_di at low-frequency (20 Hz) stimulation decreased significantly compared with the prefatigue value (P<0.05), whereas no change in P_di was observed at high-frequency (100 Hz) stimulation. In the fatigued diaphragm, P_di at both stimuli increased with an infusion of either DOA (P<0.05) or DOB (P<0.05). The increase of P_di at 20 Hz stimulation was significantly larger in the DOB group compared with that of the DOA group (P<0.05). In each group, P_di at both stimuli decreased after the cessation of administration. The integrated diaphragmatic electric activity (E_di) in the two groups did not change at any frequency of stimulation throughout the study. We conclude that DOB in comparison with DOA is more effective in improving the contractility of the fatigued diaphragm.     

Climbing exercise increases bone mass and trabecular bone turnover through transient regulation of marrow osteogenic and osteoclastogenic potentials in mice.

To investigate the relationship between the effects of bone turnover and bone marrow cell development in bone cells, we developed a mouse voluntary climbing exercise model. Climbing exercise increased bone volume and transient osteogenic potential of bone marrow. This model would be suitable for investigating the mechanistic roles of mechanical loading. INTRODUCTION: The relationship between bone mass gain and local bone formation and resorption in mechanically loaded bone is not well understood. MATERIALS AND METHODS: Sixty-five C57BL/6J mice, 8 weeks of age, were assigned to five groups: a baseline control and two groups each of ground control and climbing exercise mice for 2 and 4 weeks. Mice were housed in a 100-cm tower and had to climb toward a bottle placed at the top to drink water. RESULTS: Compared with the ground control, bone mineral density of the left femur increased in the climbing mice at 4 weeks. At 2 and 4 weeks, bone formation rate (BFR/BS) of periosteal surface, the cross-sectional area, and moment of inertia were increased in the climbing mice, whereas BFR/BS and eroded surface (ES/BS) of endosteal surface did not differ. The trabecular bone volume (BV/TV) of the proximal tibia increased in climbing mice, and osteoclast surface (Oc.S/BS) and osteoclast number decreased at 2 weeks. At 4 weeks, there were increases in BV/TV and parameters of bone formation, including mineralized surface, mineral apposition rate, and bone formation rate. In marrow cell cultures from the tibia, the number of alkaline phosphatase+ colony forming units-fibroblastic and the area of mineralized nodule formation in climbing mice were increased, and the number of osteoclast-like TRACP+ multinucleated cells was lower at 2 weeks. At 4 weeks, these parameters recovered to the levels of the ground controls. CONCLUSION: Our results indicate that climbing increased trabecular bone volume and reduced bone resorption, with a subsequent increase in bone formation. Intermittent climbing downregulates marrow osteoclastogenic cells and upregulates osteogenic cells initially, but further exercise seemed to desensitize them. Cortical envelopes were enlarged earlier, but the response seems to differ from trabecular bone.     

Trends in antihypertensive drugs used for elderly patients]

The admission of antihypertensive medications in the elderly (65 y.o. or more, 269 pts) was compared to that in younger cases (less than 65 y.o., 348 pts). All were outpatients who visited our clinic in 1990. The number of patients on a single therapeutic regimen was almost equal in both age groups. Once-a-day regimens were more common in the young (56.9% vs 48.3%, p less than 0.05), and three times-a-day regimens were more common in the elderly (14.7% vs 23.1%, p less than 0.01). The choice of antihypertensive drugs in patients with single therapy or combined therapy in the young was beta blockers in 49.7%, Ca blockers in 39.4%, diuretics in 30.7% and ACE inhibitors in 17.8%, and those in the elderly were Ca blockers in 46.1%, diuretics in 44.2%, beta blockers in 33.8%, and ACE inhibitors in 16.4%. The patients were subdivided into three groups according to the time of the initial visit to the clinic; initial visit during 1969-1979 (phase 1), 1980-1984 (phase 2) and 1985-1990 (phase 3). In the young, choice of beta blockers and diuretics was most popular in phase 1. However, the choice of diuretics decreased in phase 2, and in phase 3 beta blockers were used in 50.4%, Ca blockers in 43.2%, ACE inhibitors in 22.3% and diuretics in only 17.3%. In the elderly, diuretics were most popular followed by Ca blockers and beta blockers in phase 1 and phase 2. In phase 3 Ca blockers were selected in 58.2% followed by both beta blockers and ACE inhibitors in 28.4% then diuretics in 23.9%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhancement of hepatitis-B surface-antigen expression by 5-azacytidine in a hepatitis-B-virus-transfected cell line.

The human hepatoblastoma-derived cell line HB611 secretes hepatitis-B surface antigen (HBsAg) and hepatitis-B e antigen (HBeAg) into the medium. Hepatitis-B-virus (HBV) DNA integrated into the cellular genome was found to be hypermethylated. When the cells were treated with 5-azacytidine for 3 days, the level of HBsAg in the medium increased, while the level of HBeAg remained constant. The level of alpha-fetoprotein (AFP) decreased with the 5-azacytidine treatment. Southern blot analysis of DNA digested with HpaII or MspI showed that 5-azacytidine treatment resulted in hypomethylation of the integrated HBV DNA, suggesting that 5-azacytidine increased HBsAg production in the cells through hypomethylation of the HBV genomic DNA.     

Human urotensin-II potentiates the mitogenic effect of mildly oxidized low-density lipoprotein on vascular smooth muscle cells: comparison with other vasoactive agents and hydrogen peroxide.

Human urotensin-II (U-II) is the most potent vasoactive peptide identified to date, and may be involved in hypertension and atherosclerosis. We investigated the effects of the interactions between U-II or other vasoactive agents and mildly oxidized low-density lipoprotein (mox-LDL) or hydrogen peroxide (H2O2) on the induction of vascular smooth muscle cell (VSMC) proliferation. Growth-arrested rabbit VSMCs were incubated with vasoactive agents (U-II, endothelin-1, angiotensin-II, serotonin, or thromboxane-A2) in the presence or absence of mox-LDL or H2O2. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. On interaction with mox-LDL or H2O2, U-II induced the greatest increase in [3H]thymidine incorporation among these vasoactive agents. A low concentration of U-II (10 nmol/l) enhanced the potential mitogenic effect of low concentrations of mox-LDL (120 to 337%) and H2O2 (177 to 226%). U-II at 50 nmol/l showed the maximal mitogenic effect (161%), which was abolished by G protein inactivator (GDP-beta-S), c-Src tyrosine kinase inhibitor (radicicol), protein kinase C (PKC) inhibitor (Ro31-8220), extracellular signal-regulated kinase (ERK) kinase inhibitor (PD98059), or Rho kinase inhibitor (Y27632). Mox-LDL at 5 microg/ml showed the maximal mitogenic effect (211%), which was inhibited by free radical scavenger (catalase), intracellular and extracellular antioxidants (N-acetylcysteine and probucol), nicotinamide adenine dinucleotide phosphate oxidase inhibitor (diphenylene iodonium), or c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results suggested that U-II acts in synergy with mox-LDL in inducing VSMC DNA synthesis at the highest rate among these vasoactive agents. Activation of the G protein/c-Src/PKC/ERK and Rho kinase pathways by U-II together with the redox-sensitive JNK pathway by mox-LDL may explain the synergistic interaction between these agents.     

Case of Heerfordt's syndrome with prolonged peripheral nerve involvement]

A 28-year-old man complaining of myiodesopsia was given a diagnosis of uveitis. Subsequently he complained facial nerve palsy and enlargement of parotid gland. Heerfordt's syndrome was diagnosed based on the results of several examinations. Facial nerve palsy, enlargement of the parotid gland and uveitis were improved by systemic corticosteroid therapy. At present he is receiving systemic corticosteroid therapy, but numbness in the mouth, thought to be the involvement of the trigeminal nerve, remains. Systemic corticosteroid therapy is usually effective for most cases with Heerford's syndrome. On the other hand, there are some cases with the prolonged peripheral nerve involvement despite systemic corticosteroid therapy, as seen in this case. If peripheral nerve involvement is prolonged, it is necessary to consider small-fibre neuropathy as one possible cause.     

Effect of tacrolimus and partial hepatectomy on transthyretin metabolism in rats

Liver transplantation, which serves as treatment of familial amyloidotic polyneuropathy (FAP), and domino liver transplantation, which utilizes resected livers from patients with FAP for treatment of liver diseases, may induce changes in transthyretin (TTR), a pathogenic FAP-related protein. To evaluate this possibility, we performed a 70% hepatectomy or administered tacrolimus to Dark Agouti (DA) rats for 7 days and then measured changes in liver TTR mRNA levels and changes in serum TTR concentrations. After hepatectomy, TTR mRNA levels decreased by 77%; at day 3, they returned to preoperative levels. Except for slightly elevated serum TTR concentrations 12 h after operation, serum TTR levels remained unchanged. Thus, partial hepatectomy did not influence serum TTR concentrations. After tacrolimus administration, TTR mRNA declined by 56% 12 h after the experiment started; however, after day 3, a rebound phenomenon occurred until day 7. Tacrolimus may facilitate serum TTR degradation, although production of TTR in the liver also increased. This finding -- that TTR, the source of FAP-inducing amyloid, did not increase after transplantation -- may help post-transplantation treatment of patients who have FAP and other liver diseases.     

Cleft lip-nose repair technique: Sequential repair

The results of repairing cleft lip by aesthetic plastic surgery are now excellent. However, the cleft lipnose deformity is still very difficult to repair with the present techniques. A technique that can repair the cleft lip-nose deformity with good results is presented. The technique is divided into three parts: Part I consists of nasal repair of the primary cleft lip. Part II is nasal reconstruction as a secondary operation with or without lip repair. For example, nasal reconstruction may be secondary to repair of deformities of the sill, rim, limen nasi, septum, or nasal bones. Part III is an aesthetic nasal operation such as rhinoplasty, mentoplasty, or zygomaplasty.     

Somatosensory and spinal evoked potentials in patients with cervical syringomyelia.

We recorded somatosensory evoked potentials (SEPs) from the skin surface and spinal evoked potentials (SpEP) from the posterior epidural space after median nerve stimulation in 11 patients with cervical syringomyelia. We compared SEPs with SpEP to assess the possible feasibility of using these techniques to localize the offending lesion. SEP abnormalities were present on one or both sides of 7 patients (9 of 22 upper limbs; 41%). The abnormal SEP pattern was the attenuation or loss of N13, which was of little value for delineating the lesion. In patients with abnormal SEPs, three types of abnormal SpEPs were noted. In the Type A abnormality (three limbs), potentials were attenuated in all cervical segments, suggesting that the syrinx itself had enlarged to involve the posterior column. In Type B (two limbs), there was reduced amplitude or absent upper cervical potentials, probably a result of the accompanying tonsilar herniation. Finally, the Type C (four limbs) abnormality was a mixture of Type A and B abnormalities in that the attenuated cervical potentials were again affected in the most upper cervical segment. We concluded that SpEP revealed various kinds of involvement of the dorsal column pathway in the syringomyelic patients, a finding not expressed with conventional SEPs.