Protective effects of serotonin reuptake inhibitors, citalopram and clomipramine, against hippocampal CA1 neuronal damage following transient ischemia in the gerbil

To clarify the role of serotonin in cerebral ischemia, we examined the effects of selective serotonin reuptake inhibitors, citalopram and clomipramine, on ischemic neuronal damage in the gerbil. Pretreatment with citalopram (40 mg/kg i.p.) and clomipramine (20 mg/kg i.p.) protected against neuronal destruction of hippocampal CA1 pyramidal cells following 5 min of forebrain ischemia. Furthermore, microdialysis assays showed that a striking increase in extracellular excitatory amino acid levels during ischemia was significantly inhibited by pretreatment with citalopram and clomipramine. However, citalopram (40 mg/kg i.p.) did not alter the extracellular amino acid concentrations in normal gerbils. Thus, serotonin reuptake inhibitors have a protective effect against ischemic neuronal damage. Furthermore, the present result suggests that the protective effect is mediated through prevention of the accumulation of extracellular excitatory amino acids during and after ischemia.     

TNF-alpha augments the expression of RhoA in the rat bronchus.

While nonspecific airway hyperresponsiveness (AHR) is a central feature of allergic bronchial asthma, the mechanism underlying the development of AHR is not clearly understood. We have previously demonstrated in vitro hyperresponsiveness of bronchial smooth muscle to acetylcholine (ACh) in rats that were actively sensitized and repeatedly challenged with aerosolized antigen. It has also been demonstrated that the ACh-induced, RhoA-mediated Ca(2+) sensitization is markedly augmented concomitantly with an increased expression and activation of RhoA protein in the bronchial smooth muscle of the antigen-treated rats. In the present study, we have investigated whether TNF-alpha, a proinflammatory cytokine which is involved in bronchial asthma, causes upregulation of RhoA mRNA and protein in the rat bronchus. Treatment of rat bronchial smooth muscle preparations with TNF-alpha (300 ng/ml for 24 hr) significantly shifted the concentration-response curve to ACh upwards, but did not alter the response to high K(+), when compared to that of control tissues. Levels of RhoA mRNA and protein in the TNF-alpha-treated bronchus were significantly greater than those in the control group. In conclusion, it is suggested that the augmentation of the ACh-induced contractile response evoked by TNF-alpha might be mediated by an upregulation of RhoA in rat bronchial smooth muscle.     

Rheumatoid arthritis in patients aged above 75 years old at onset]

Elderly onset rheumatoid arthritis (RA) is difficult to diagnose definitively when the patients note their first symptoms of arthritis above the age of 75 years old. In this report, we reviewed the clinical features of elderly onset RA and its diagnosis. The subjects included 4 females, aged 78, 83, 84 and 93 years, respectively. The onsets were abrupt in 2 cases and more slowly arriving in the other 2. Shoulder joints and wrist joints were involved in all cases. Knee joints, finger joints and foot joints were involved in 3 cases and the elbow was involved in one case. Anti-RA treatment quickly attenuated the acute and severe arthritis and brought down the high CRP level associated with vivid inflammatory activity of RA. The RAPA value was very high in all but one of the cases. Severe destructive findings in radiography was undetectable in the major joints (e.g. shoulder, hip and knee joints). Radiographic findings in wrist and finger joints were also very difficult to differentiate from arthrosis and osteoporosis. On the other hand, RA involvement in the cervical spine was certain in the radiographs; 1 case had anterior atlantoaxial subluxation and 2 cases had subaxial intervertebral erosion. Pathological radiographic findings in the cervical spine are useful for the diagnosis of elderly onset RA.     

Potentiating effects of extraluminal oxyhemoglobin to intraluminal 5-hydroxytryptamine in isolated canine internal carotid arteries

The interaction between oxyhemoglobin (oxyHb) and 5-hydroxytryptamine (5-HT) was investigated in an experimental model of isolated canine internal and common carotid arteries with insertion of stainless steel cannulae. Extraluminal application of 10(-5) M oxyHb induced marked and long-lasting vasoconstriction in the internal carotid but not in the common carotid arteries. The 5-HT-induced vasoconstriction was potentiated significantly in both the internal and common carotid arteries. These potentiations were not influenced by the presence or absence of endothelium, a finding which was confirmed by vascular responses to intraluminal acetylcholine. It is concluded that the interaction between extraluminal oxyHb and intraluminal 5-HT may be one of the possible etiological factors behind the chronic phase of vascular spasm following subarachnoid hemorrhage.     

Solitary right ventricle metastasis by renal cell carcinoma.

A 57-year-old man with a history of renal cell carcinoma presented with presyncope. He underwent nephrectomy years earlier followed by HLA-matched allogeneic peripheral-blood stem-cell transplantation. Echocardiographic investigation revealed a solitary right ventricle mass without contiguous vena caval or right atrial involvement. The mass was pathologically confirmed to be metastatic carcinoma in the right ventricular cavity. This case highlights the need to consider an underlying neoplastic syndrome in patients presenting isolated right ventricle mass by echocardiography.     

Surgical treatment of pseudoaneurysm of the sinus of valsalva after aortic valve replacement for active infective endocarditis.

Pseudoaneurysm is an uncommon and serious complication of infective endocarditis (IE). It is often fatal because of its rapid progress, high rates of rupture and recurrence, and worsening effects on the systemic condition. We report the rare case of a patient who developed a pseudoaneurysm of the sinus of Valsalva two months after emergency aortic valve replacement for active IE. At the previous operation, we had directly closed a small fistulous hole in the non-coronary sinus of Valsalva using two mattress sutures with autologous pericardial pledgets, because the tissue surrounding the hole did not appear to be infected on visual inspection. A pseudoaneurysm developed from this portion due to detachment of sutures. If the fistula had been completely resected during the first surgery instead of performing a simple closure, the pseudoaneurysm of the sinus of Valsalva would not have formed. However, the primary aim of the first emergency surgery was to spare the life of a critically ill patient. In the second surgery, the pseudoaneurysm was completely resected with the aortic wall--including the non-coronary sinus of Valsalva and the communicating hole. Then, patch plasty of the non-Valsalva sinus was successfully performed.     

Analysis of the non-sense mutants of varicella-zoster virus thymidine kinase

Summary.  Three non-sense mutants of varicella-zoster virus (VZV) thymidine kinase (TK) gene, VZTK₃₂₅, VZTK₂₇₈ and VZTK₂₂₄, were isolated. The mutants had a single nucleotide substitution at codons 326, 279 and 225, which changed the codon of TGG (tryptophan) to the stop codon TGA. The wild type (WT) and mutant TKs were expressed in E. coli cells and their characteristics were evaluated. VZTK₂₂₄ lost TK activity, but VZTK₃₂₅ and VZTK₂₇₈ maintained 74.8% and 21.2% of the WT TK activity. On the other hand, all mutants lost the thymidylate kinase activity. Moreover, VZTK₃₂₅ and VZTK₂₇₈ polypeptides were heat-labile. These data suggest that the carboxy-terminal portion of herpesvirus TK plays an important role in the stable folding of TK and thymidylate kinase activity. Received April 21, 1997 Accepted June 16, 1997     

Bacterial superantigen enhances cytokine production by T-helper lymphocyte subset-2 cells and modifies glomerular lesions in experimental immunoglobulin a nephropathy

Background The purpose of this study was to examine the effects of bacterial suporantigens, which can derange the immune response and contribute to the renal lesions of immunoglobulin A (lgA) nephropathy. Methods Twenty-five micrograms of a bacterial superantigen, staphylococcal enterotoxin B (SEB), was injected into IgA nephropathy-prone ddY mice intrathymically when they reached 6 weeks of age. Evaluation included measurement of albumin excretion in urine, immunoglobulin concentration, and lymphokine production in vitro, as well as analysis of T-cell receptor expression in splenic T-cell subsets and examination of renal histology by light and fluorescence microscopy. Results At 40 weeks of age, the serum level of IgA in these mice was substantially increased and the number of Vβ8⁺ CD4⁺splenic T-cells was significantly decreased compared with measurements in untreated controls. Both control and SEB-treated mice excreted less than 30 μg/mL of urinary albumin. In mice given SEB, the amount of interleukin 2 (IL-2) and tumor necrosis factor-α (T helper 1 [Th1]-type cytokines) produced by the in vitro-stimulated lymphocytes significantly decreased. whereas that of interleukin 4 (IL-4) and interleukin 6 (IL-6) (Th2-type cytokines) markedly increased compared with measurements in control mice. At 40 weeks of age, mice given SEB showed marked glomerular hypercellularity and enhanced glomerular C3 deposition by renal histology, compared with control mice. Conclusion These results suggest that bacterial superantigen SEB may modify glomerular lesions through activating Th2 cells, while inducing deletion of Th1 cells in this experimental model.     

Responses of isolated canine ophthalmic and ciliary arteries to vasoactive substances

The effects of 11 vasoactive substances were compared on the isolated and perfused canine internal and external ophthalmic and ciliary arteries. The vessels were isolated with the optic nerve, and perfused independently with Tyrode solution under a constant flow rate at 37 degrees C and a perfusion pressure of 40-80 mmHg. Drugs used were 5-hydroxytryptamine (5-HT), epinephrine (EPI), norepinephrine (NE), phenylephrine (PHE), prostaglandin F2 alpha (PGF2 alpha), ATP, dopamine (DA), tyramine (TYR), KCl, xylazine (XYL) and clonidine (CLO). Each drug solution was administered by a microinjector into the endothelial side of an artery through a cannula. Responses were obtained as changes in perfusion pressure. Results were as follows: 1) The rank order of potency for inducing a vasoconstriction in external ophthalmic arteries (EOA) was 5-HT greater than or equal to EPI greater than NE greater than PHE much greater than ATP greater than or equal to DA greater than KCl much much greater than TYR, XYL, CLO. Since PGF2 alpha induced only a slight vasoconstriction, it was omitted from the order. 2) In internal ophthalmic arteries (IOA), the responses were similar to those in EOA, although EPI, NE and PHE induced a relatively smaller response. The order was 5-HT greater than EPI = NE greater than PHE much greater than DA = ATP greater than KCl much much greater than TYR, XYL, CLO. 3) In ciliary arteries, the order was EPI greater than NE greater than PHE greater than PGF2 alpha greater than DA greater than ATP greater than KCl much much greater than TYR, XYL, CLO. It was found that 5-HT induced a slight vasoconstriction and the efficacy was low. PGF2 alpha induced a greater response in ciliary arteries than in EOA or IOA. 4) In all three arteries, alpha-2 adrenoceptor agonists, XYL and CLO did not produce significant changes in perfusion pressure. These three arteries might be rich in alpha-1 adrenoceptors but poor in alpha-2 adrenoceptors.     

Clinical evaluation of cefmenoxime in internal medicine, with special reference to infection associated with hematological disorders

Clinical evaluation of cefmenoxime (CMX, Bestcall) was performed against infections associated with hematological, respiratory tract and other disorders. Clinical effectiveness of CMX against severe infections with hematological disorders including sepsis, pneumonia, pyelitis and so on was 74.4% for good responses and against the respiratory tract infections, 96.2% for good responses was obtained. Neither objective or subjective side effects nor extreme abnormalities in laboratory tests were observed in these patients. It can be concluded, therefore, that CMX is one of the most useful drugs against infectious diseases associated with hematological disorders, respiratory tract and other disorders.