Effects of local administrations of tempol and diethyldithio-carbamic on peripheral nerve activity

We have recently shown that systemic administration of a superoxide dismutase mimetic, tempol, resulted in decreases in mean arterial pressure and heart rate along with a reduction in renal sympathetic nerve activity (RSNA). It has also been shown that these parameters are significantly increased by systemic administration of a superoxide dismutase inhibitor, diethyldithio-carbamic (DETC), indicating a potential role of reactive oxygen species in the regulation of RSNA. In this study, we examined the effects of local administrations of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) and DETC on RSNA in anesthetized rats. Either tempol or DETC was directly administered onto the renal sympathetic nerves located between the electrode and ganglion. Local application of tempol (10 microL, 0.17 to 1.7 mol/L, n=6) resulted in dose-dependent decreases in integrated RSNA (by -81+/-6% at 1.7 mol/L) without alterations in mean arterial pressure and heart rate. In contrast, DETC (10 microL, 0.17 to 1.7 mol/L, n=6) increased RSNA dose-dependently. The responses of RSNA to tempol and DETC were significantly greater in spontaneously hypertensive rats than in normotensive rats (n=6, respectively). Local application of sodium nitroprusside (1 mmol/L) or N(G)-nitro-L-arginine methyl ester (0.11 mol/L) altered neither basal RSNA nor tempol-induced reductions in RSNA (n=6 and 5, respectively). A voltage-gated potassium channel blocker, 4-aminopyridine (0.1 mol/L), significantly decreased basal RSNA (by -81+/-1%) and completely prevented DETC-induced increases in RSNA (n=5). These results suggest that reactive oxygen species play a role in the regulation of peripheral sympathetic nerve activity, and that at least part of this mechanism is mediated through voltage-gated potassium channels.     

Melanotic oncocytic metaplasia of the nasopharynx: a case report with a focus on immunohistochemical analyses and literature review

Melanotic oncocytic metaplasia (MOM) of the nasopharynx is an extremely rare lesion, with only 21 cases reported in English literature to date. MOM typically occurs near the Eustachian tube opening in Asian men in their 60 s to 70 s. Here, we present a case of MOM in a 57-year-old Japanese man who is a heavy smoker. The patient did not have complaints; MOM was diagnosed incidentally as 4 flat elevated lesions with brown to black discoloration, ranging from 2 to 3 mm in maximal diameter, were found in the right torus tubarius. On suspecting melanoma, the largest lesion was biopsied. Microscopic examination identified both oncocytic metaplasia and melanin pigmentation of the epithelium in the same gland. Upon immunohistochemical examination, melanocytes displayed reactivity for 3 out of 4 melanocytic markers; immunopositivity for S-100 protein, Melan-A, and MITF and immunonegativity for HMB-45 was observed. Normal melanocytes in the nearby surface respiratory epithelium displayed the same pattern of immunoreactivity. Immunopositivity for S-100 protein and immunonegativity for HMB-45 have been previously reported in MOM. Reduction of stimulation of melanocytes in a longstanding lesion like MOM may explain the immunonegativity for HMB-45. S-100 protein, in conjunction with more specific marker for melanocytes, Melan-A or MITF, could prove the definite presence of melanocytes in this case of MOM. As it has been shown by previous reports that MOM pursues a benign course, it will be sufficient to follow up the patients regularly for the remaining 3 lesions.     

Usefulness of pet ownership as a modulator of cardiac autonomic imbalance in patients with diabetes mellitus, hypertension, and/or hyperlipidemia

Among patients with coronary artery disease, pet owners exhibit a greater 1-year survival rate than nonowners. Lifestyle-related diseases are well-known risk factors for coronary artery disease and induce imbalances in autonomic nervous activity. The purpose of the present study was to determine whether pet ownership modulates cardiac autonomic nervous activity imbalance in patients with lifestyle-related diseases such as diabetes mellitus, hypertension, and hyperlipidemia. A total of 191 patients (mean age 69 ± 8 years) were interviewed about their pet ownership status and were classified into pet owner and nonowner groups. After recording a 24-hour Holter electrocardiogram for heart rate variability analysis, frequency-domain and nonlinear-domain analyses were performed to determine the high-frequency (HF) and low-frequency (LF) components, LF/HF ratio, and entropy. The heart rate variability parameters were assessed for 24 hours, during the day (8.00 A.M. to 5.00 P.M.), and during the night (0:00 A.M. to 6.00 A.M.), and compared between the 2 groups. To evaluate the potential predictive factors for cardiac autonomic imbalance, univariate and multivariate analyses of HF and LF/HF were conducted for potential confounding variables. The pet owner group exhibited significantly greater HF(24h), HF(day), HF(night), entropy(24h), entropy(day), and entropy(night) and significantly lower LF/HF(24h) and LF/HF(night) compared to the nonowner group. On multivariate analysis, pet ownership was independently and positively associated with HF(24h,) HF(day), and HF(night) and inversely associated with LF/HF(24h) and LF/HF(night). In conclusion, these results suggest that pet ownership is an independent modulator of cardiac autonomic imbalance in patients with lifestyle-related diseases.     

Successful Treatment of γ-Heavy-Chain Disease with Rituximab and Fludarabine

An 84-year-old Japanese man was admitted because of pancytopenia. The bone marrow was hypoplastic with a predominance of abnormal small lymphocytes and grape cells, which were positive for CD19 and CD20, and partially for the surface ?-light chain. Systemic CT scanning showed neither lymph node swelling nor hepatosplenomegaly. Serum immunoelectrophoresis and rocket immunoselection assays showed the presence of monoclonal IgG protein without a corresponding light chain and faint IgM? monoclonal protein. Histologic analysis of the clot preparation of the bone marrow aspirate facilitated a diagnosis of lymphoplasmacytic lymphoma (LPL). PCR analysis of the marrow cells demonstrated a clonal rearrangement of the immunoglobulin heavy-chain gene. From these results, we made a final diagnosis of γ-heavy-chain disease (γ-HCD) with underlying LPL localized in the bone marrow. We performed only a single course of immunochemotherapy (rituximab and fludarabine) in view of severely impaired hematopoiesis, which resulted in marked reduction of lymphoma cells and improvement of hematopoiesis. This report suggests the efficacy of rituximab plus fludarabine therapy for LPL-associated γ-HCD.     

Range of Motion of the Temporomandibular Joint in Rheumatoid Arthritis: Relationship to the Severity of Disease

The purpose of this study was to determine the frequency and nature of temporomandibular joint (TMJ) involvement in rheumatoid arthritis (RA) patients with symptoms in this joint, and to investigate the relationship of symptoms to the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and Steinbrocker stage. Clinical examination of the range of motion of the TMJ was performed in 218 RA patients. In addition, correlations between the maximal mouth opening and the severity of RA were studied. Restriction in opening the mouth (defined as ≤ 30 mm movement in the central incisor region from the fully occluded to maximally open positions) was observed in 12.8% of the RA patients (28/218). The CRP, ESR and Steinbrocker stage were all correlated with maximal opening (p < 0.05). There was a positive correlation between the severity of RA and the range of motion of the jaw.