Transcranial magnetic stimulation of the facial nerve]

It was the object of the present study to determine whether transcranial facial nerve stimulation using a magnetic coil can be clinically applicable, and to find the site where the facial nerve is best stimulated. A magnetic coil was placed over the parieto-occipital skull of the subjects for stimulation, and the facial nerve was electrically stimulated in its intracranial and peripheral courses. Then an electromyogram was recorded from the nasalis muscle of the face on the stimulated side. In 9 healthy volunteers, 18 facial nerves received magnetic and electric stimuli in the peripheral region, and the actual site of stimulation was estimated from the conduction velocity of the nerve. The conduction velocity was 56.6 +/- 4.8 m/s, and the latency between CMAPs for electric at the magnetic stimuli to the posterior tragus was 1.23 +/- 0.21 ms. Therefore, the position stimulated by magnetic coil was estimated to be 70.0 +/- 11.4 mm central to the posterior tragus, i.e., near the root exit zone. In two patients undergoing surgery in the cerebellopontine angle, transcranial magnetic stimulation and electrical stimulation of the intracranial facial nerve were compared intraoperatively. The CMAP produced by transcranial magnetic stimulation coincided closely with that produced by direct electrical stimulation of the root exit zone. Thus, the facial nerve was stimulated at the root exit zone, and this method could be expected to be useful for evaluation of disorders of the intracranial facial nerve.     

DNA microarray analysis of white adipose tissue from obese (fa/fa) Zucker rats treated with a beta3-adrenoceptor agonist, KTO-7924.

We aimed to examine the effects of KTO-7924 (beta3-adrenoceptor agonist) on lipid metabolism and mRNA expressions in retroperitoneal white adipose tissue (RP WAT) in obese (fa/fa) Zucker rats using DNA microarray. Oral KTO-7924 for 28 days significantly decreased RP WAT weight, plasma triglyceride, free fatty acid, and insulin, and improved insulin resistance in oral glucose tolerance tests. In RP WAT of KTO-7924-treated rats, DNA microarray analysis revealed specifically enhanced mRNA expressions of uncoupling protein 1 (UCP1) and cytochrome c oxidase subunit VIII-H (COX8H), which are reportedly highly expressed in brown adipose tissue (BAT). Since these mRNA expression levels in RP WAT were significantly lower in obese (fa/fa) Zucker rats than in lean Zucker rats, these genes may be important in lipid metabolism. Our results imply that in obese (fa/fa) Zucker rats, continuous stimulation of beta3-adrenoceptors by KTO-7924 causes BAT-like adipocytes to appear in RP WAT, and improves lipid metabolism.     

Hyperbaric exposure with high oxygen concentration enhances oxidative capacity of neuromuscular units

The effects of hyperbaric exposure with high oxygen concentration on spinal motoneurons and the skeletal muscle fibers that they innervate were investigated. Five-week-old male rats were exposed to a hyperbaric (1.25 atmospheric pressure) environment with a high oxygen concentration (35.0%) for 6h daily. The number, cell body size, and oxidative enzyme activity of motoneurons innervating the soleus and plantaris muscles were examined after 8 weeks of hyperbaric exposure. In addition, the fiber type distribution, cell size, and oxidative enzyme activity of the slow soleus and fast plantaris muscles were examined. The oxidative enzyme activity of alpha motoneurons innervating the soleus and plantaris muscles increased after hyperbaric exposure, irrespective of their cell body sizes. The percentage of high-oxidative fibers in the soleus and plantaris muscles increased after hyperbaric exposure. The oxidative enzyme activity of all types of fibers in the soleus and plantaris muscles increased after hyperbaric exposure. It is concluded that hyperbaric exposure with high oxygen concentration enhances the oxidative capacity of neuromuscular units.     

Marked induction of gelatinases,especially type B,in host fibroblasts by human ovarian cancer cells in athymic mice

Two human ovarian adenocarcinoma cell lines, MCAS-3 and OVISE-3 were found to secrete little of any type of gelatinase in tissue culture. However, when these cell lines were implanted subcutaneously into nude mice the cyst fluids from the resultant tumors contained gelatinase A and/or B. The enzyme activities, especially of gelatinase B, were much higher in the malignant MCAS-3 tumors than in those of the less malignant OVISE-3 tumor cells. To elucidate the origin of gelatinase B in cyst fluids of the MCAS-3 tumors, murine skin fibroblasts (MSF) were isolated from a subcutaneous tumor in a nude mouse and tested for their proteinase secretion in culture. MSF cells, which secreted some gelatinase A and gelatinase B, were induced to secrete high levels of both enzymes, especially gelatinase B, by co-cultivation with MCAS-3 cells. In addition, gelatinase A activity was induced by incubation of MSF cells with the conditioned medium of either MCAS-3 or OVISE-3 cells, whereas gelatinase B was induced only with that of MCAS-3. Although cytokines or growth factors such as IL-1 TGF-1, TNF- or EGF stimulated the secretion of gelatinases A and B from MSF cells, their effects on gelatinase B activity were far less than that of the MCAS-3 conditioned medium. These results indicate that the major part of gelatinase B activity in the cyst fluids of the ovarian tumors is secreted by host interstitial cells stimulated by tumor-derived humoral factors. Similar tumor cell-host cell interactions may be important in the production of various proteinases in other tumor types.     

Influence of antigenic forms and adjuvants on the IgG subclass antibody response to Aujeszky's disease virus in mice.

The influence of antigenic forms of Aujeszky's disease virus (ADV) and adjuvant types on the production of IgG subclass antibodies in mice was investigated. Particulate antigen, inactivated ADV, alone induced IgG1 and lower IgG2a antibody production, while the antigen adsorbed onto aluminum phosphate gel (alum) enhanced IgG1 antibody production but suppressed IgG2a antibody production as well as solubilized ADV antigen adsorbed onto alum. QS21 saponin purified from Quillaja saponaria promoted the production of IgG1 and IgG2a antibodies in a large extent against the both particulate and soluble antigens, while this saponin has strong hemolytic activity. Lablaboside F saponin isolated from Dolichos lablab without hemolytic activity, also induced the production of large IgG1 and little IgG2a antibody against both antigens. Oil-based adjuvant, ISA70 of water-in-oil type and ISA25 of oil-in-water type, increased IgG1 and IgG2a antibodies against the both soluble and particulate antigens, whereas a combination of ISA25 and soluble antigen reduced IgG2a antibody response. These results indicate that IgG1 antibody production was not suppressed by a combination of antigenic form and adjuvant type, however, IgG2a antibody production was influenced.     

Extradural total petrous apex resection with trigeminal translocation for improved exposure of the posterior cavernous sinus and petroclival region

We have analyzed a strategy for improved exposure of the posterior cavernous sinus and petroclival region through an extradural subtemporal approach to be utilized in the removal of neoplastic processes with involvement of the apical petrous bone and posterior cavernous sinus. This surgical approach includes the following elements for improved exposure of the posterior cavernous sinus through the middle fossa corridor: (1) maximal extradural exposure and mobilization of the trigeminal nerve complex, allowing its elevation and anterior displacement, (2) complete extradural removal of the anterior petrous pyramid from the porus acousticus to the petrous apex under direct vision, (3) total exposure of the abducens nerve from the posterior fossa to its point of cross over the intracavernous carotid artery, and (4) wide extradural exposure of the cavernous carotid artery in the foramen lacerum region. This strategy can be combined with other related approaches; specifically, frontotemporal or posterior transpetrosal exposures for extensive lesions.Microsurgical dissection and morphometric analysis were performed in 20 fixed cadaver specimens for the purposes of validating the method for clinical application and determining the key elements to maximization of exposure. The trigeminal complex could be anteromedially retracted 4.8 mm +/- 1.3 (range = 3 to 6 mm) without skeletonization of V(2) and V(3). Liberating these two divisions from their bony canals to their first peripheral branch (10.4 mm +/- 2.5 and 5.4 mm +/- 1.1, respectively) resulted in increased mobilization an average of 9.1 mm +/- 1.7 (7 to 14 mm). Further mobilization is achieved by dividing the attachment between the trigeminal connective tissue sheath and the fibrous carotid ring at the foramen lacerum. An average of 13.0 mm +/- 3.1 (7 to 20 mm) of the posterior intracavernous carotid artery was exposed. Detailed microanatomic observations and a comprehensive morphometric analysis of the relevant anatomic relationships were made.     

Study of the distribution by age group of serum cross-linked C-terminal telopeptide of type I collagen and procollagen type I N-propeptide in healthy Japanese women to establish reference values

Osteoporosis prevention is an important public health goal. Bone turnover markers are clinically measured to assess bone strength. C-terminal telopeptide of type I collagen (CTX) is released when collagens degrade and serves as an indicator of bone resorption. Simple CTX immunoassays are now available. However, serum CTX (sCTX) reference ranges for Japanese women are lacking. Procollagen type I N-propeptide (intact P1NP) reflects osteoblast activity, serving as a marker of bone formation. Because sCTX and intact P1NP are clinically applied as bone turnover markers, we determined reference ranges for both sCTX and intact P1NP in healthy Japanese women. We collected 228 blood samples from healthy Japanese women aged 19–83 years, grouped by age and menopausal status. We measured sCTX and intact P1NP and examined their correlation. sCTX values differed significantly between the two consecutive decade groups encompassing 19–39 years of age, intact P1NP values between 20 and 30 s, between post-menopausal 50 and 60 s, and between pre-and post-menopausal women in their 50 s. The mean sCTX of 91 healthy pre-menopausal women was 0.255 (0.100–0.653) ng/mL, the intact P1NP in 90 women 33.2 (17.1–64.7) μg/L. Corresponding values for post-menopausal women were 0.345 (0.115–1.030) ng/mL and 41.6 (21.9–79.1) μg/L. sCTX correlated with intact P1NP. Bone resorption markers are measured to assess anti-resorption agents, bone formation markers to assess the effects of bone-forming agents. The sCTX and intact P1NP reference values determined herein, in healthy Japanese women, are expected to be useful for osteoporosis treatment, assessment of fracture risk, and other clinical applications.     

An Exploratory Study of Dapagliflozin for the Attenuation of Albuminuria in Patients with Heart Failure and Type 2 Diabetes Mellitus (DAPPER)

Background and Aims

Sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, which are anti-diabetic drugs, reportedly decrease the incidence of cardiovascular events in high-risk patients with cardiovascular diseases, and thus chronic heart failure (CHF). SGLT-2 inhibitors also decrease albuminuria in patients with type 2 diabetes mellitus (T2D). Since albuminuria is a biomarker of not only chronic kidney disease but also cardiovascular events, we hypothesized that, among T2D patients with CHF, SGLT-2 inhibitors will decrease the extent of albuminuria and also improve CHF concomitantly.

Methods

DAPPER (UMIN000025102) is a multicenter, randomized, open-labeled, parallel-group, standard treatment-controlled study, which is designed to evaluate whether dapagliflozin, one of the SGLT-2 inhibitors, decreases albuminuria in T2D patients with CHF and exerts cardioprotective effects on the failing heart. The patients are randomized to either of the dapagliflozin (5 or 10 mg, once daily orally) or control group (administration of anti-diabetic drugs administered other than SGLT 2 inhibitors). The estimated number of patients that need to be enrolled is 446 in total (223 in each group). The primary objective is the changes in the urinary albumin-to-creatinine ratio from the baseline after 2-year treatment. The key secondary objectives are (1) the safety of dapagliflozin and (2) the cardiovascular and renal efficacies of dapagliflozin.

Conclusion and Perspectives

DAPPER study investigates whether dapagliflozin decreases albuminuria and exerts beneficial effects on the failing heart in T2D patients. (UMIN000025102).

     

Plasma atrial natriuretic peptide concentration inversely correlates with left atrial collagen volume fraction in patients with atrial fibrillation: plasma ANP as a possible biochemical marker to predict the outcome of the maze procedure.

OBJECTIVES: We hypothesized that the plasma atrial natriuretic peptide (ANP) level reflects atrial degenerative change and may predict the outcome of the maze procedure. BACKGROUND: Although a larger preoperative left atrial dimension and longer duration of atrial fibrillation (AF) have been reported in patients with persistent AF than in those with sinus rhythm (SR), these individual factors were not enough to predict the outcome of the maze procedure. METHODS: Preoperative plasma ANP levels were measured in consecutive 62 patients who underwent the Kosakai's modified maze procedure. Moreover, we performed histological and molecular biological examinations in the resected left atrial tissues. RESULTS: The preoperative plasma ANP was lower in the AF group (n = 13) than it was in the SR group (n = 49) (p < 0.001). Multiple logistic regression analysis revealed that duration of AF and plasma ANP were independently associated with postoperative cardiac rhythm. Among 41 patients with a higher plasma ANP or shorter duration of AF than the median value, SR was restored in 95% of patients. In contrast, in 21 patients with a lower plasma ANP and a longer duration of AF than the median value, SR was restored only in 48% of patients. Histological examination revealed that the collagen volume in the left atrial tissue was higher in AF than it was in SR and inversely correlated with plasma ANP. In addition, the messenger RNA expressions of ANP, collagen type I and type III were lower in AF than they were in SR. CONCLUSIONS: These results suggest that a combination of plasma ANP and/or duration of AF may predict the success rate for the maze operation. Advanced atrial degenerative change may result in a decrease of atrial ANP secretion.     

Acute respiratory failure due to thyroid storm developing immediately after delivery

Acute respiratory failure occurs in less than 0.1% of pregnancies. Thyroid storm should be included in the differential diagnosis of possible causes of acute respiratory failure occurring immediately after delivery, and delivery is a high risk factor for thyroid storm in pregnant women with thyrotoxicosis.