Biomechanical analysis of the effect of congruence, depth and radius on the stability ratio of a simplistic 'ball-and-socket' joint model.

OBJECTIVES: The bony shoulder stability ratio (BSSR) allows for quantification of the bony stabilisers in vivo. We aimed to biomechanically validate the BSSR, determine whether joint incongruence affects the stability ratio (SR) of a shoulder model, and determine the correct parameters (glenoid concavity versus humeral head radius) for calculation of the BSSR in vivo. METHODS: Four polyethylene balls (radii: 19.1 mm to 38.1 mm) were used to mould four fitting sockets in four different depths (3.2 mm to 19.1mm). The SR was measured in biomechanical congruent and incongruent experimental series. The experimental SR of a congruent system was compared with the calculated SR based on the BSSR approach. Differences in SR between congruent and incongruent experimental conditions were quantified. Finally, the experimental SR was compared with either calculated SR based on the socket concavity or plastic ball radius. RESULTS: The experimental SR is comparable with the calculated SR (mean difference 10%, sd 8%; relative values). The experimental incongruence study observed almost no differences (2%, sd 2%). The calculated SR on the basis of the socket concavity radius is superior in predicting the experimental SR (mean difference 10%, sd 9%) compared with the calculated SR based on the plastic ball radius (mean difference 42%, sd 55%). CONCLUSION: The present biomechanical investigation confirmed the validity of the BSSR. Incongruence has no significant effect on the SR of a shoulder model. In the event of an incongruent system, the calculation of the BSSR on the basis of the glenoid concavity radius is recommended.Cite this article: L. Ernstbrunner, J-D. Werthel, T. Hatta, A. R. Thoreson, H. Resch, K-N. An, P. Moroder. Biomechanical analysis of the effect of congruence, depth and radius on the stability ratio of a simplistic 'ball-and-socket' joint model. Bone Joint Res 2016;5:453-460. DOI: 10.1302/2046-3758.510.BJR-2016-0078.R1.

Comparative study of treatment for distal radius fractures with two different palmar locking plates.

Few randomized trials have shown how the placement of a palmar locking plate affects outcomes. The purpose of this study was to compare clinical and radiological outcomes of fixation using locking plates with different concepts for placement relative to the watershed line in a prospective randomized trial. Sixty-four patients with a displaced distal radius fracture were divided into two groups according to the plates used for fixation: distal-type (AcuLoc(TM), Group A) and proximal-type (VariAx(TM), Group V). Wrist function including the range of motion and grip strength was compared at 1, 2, 3 and 6 months postoperatively. Loss of reduction was assessed radiologically. Both groups demonstrated overall satisfactory function at 6 months with no significant difference found between the groups. Minimal loss of reduction was demonstrated in both groups. Internal fixation using the palmar locking plates with two different placements provided satisfactory outcomes at 6-month follow-up, but our results indicate that plates placed distal to the watershed line may delay recovery of wrist motion.

Element specificity of ortho-positronium annihilation for alkali-metal loaded SiO2 glasses.

Momentum distributions associated with ortho-positronium (o-Ps) pick-off annihilation photon are often influenced by light elements, as, e.g., carbon, oxygen, and fluorine. This phenomenon, so-called element specificity of o-Ps pick-off annihilation, has been utilized for studying the elemental environment around the open spaces. To gain an insight into the element specificity of o-Ps pick-off annihilation, the chemical shift of oxygen 1s binding energy and the momentum distributions associated with o-Ps pick-off annihilation were systematically investigated for alkali-metal loaded SiO2 glasses by means of X-ray photoelectron spectroscopy and positron-age-momentum correlation spectroscopy, respectively. Alkali metals introduced into the open spaces surrounded by oxygen atoms cause charge transfer from alkali metals to oxygen atoms, leading to the lower chemical shift for the oxygen 1s binding energy. The momentum distribution of o-Ps localized into the open spaces is found to be closely correlated with the oxygen 1s chemical shift. This correlation with the deepest 1s energy level evidences that the element specificity of o-Ps originates from pick-off annihilation with orbital electrons, i.e., dominantly with oxygen 2p valence electrons and s electrons with lower probability.

Switching to an L/N-type calcium channel blocker shows renoprotective effects in patients with chronic kidney disease: the Kyoto Cilnidipine Study.

OBJECTIVE: This open-label, randomized controlled trial investigated the effects of cilnidipine, an L/N-type calcium channel blocker (CCB), in patients with chronic kidney disease (CKD). METHODS: Sixty patients with CKD and well-controlled hypertension being treated with a renin- angiotensin system (RAS) inhibitor and an L-type CCB (L-CCB) were randomly assigned either to switch from the L-CCB to cilnidipine after a 4-week observation period or to continue with L-CCB treatment. Blood pressure, heart rate and renal function were monitored for 12 months. Data were available for analysis from 50 patients: 24 from the cilnidipine group and 26 from the L-CCB group. RESULTS: Blood pressure was well controlled in both groups. After 12 months, proteinuria and heart rate were significantly decreased in the cilnidipine group, but proteinuria increased and heart rate remained unchanged in the L-CCB group. There was a significant positive correlation between the percentage changes in proteinuria and heart rate. CONCLUSIONS: Cilnidipine has antihypertensive effects equivalent to those of L-CCBs. In patients with CKD, proteinuria can be decreased by switching from an L-CCB to cilnidipine, thereby improving renal function.

Expression pattern of Galectin 4 in rat placentation.

Galectin 4 (Gal4) is abundantly expressed in the epithelium of the gastrointestinal tract, and functional analysis has concentrated on its roles associated with polarized membrane trafficking. This study aimed to investigate the expression of Gal4 in placentation. The expression level of Gal4 was revealed to be lower in differentiated Rcho-1 cells (a model system of rat trophoblast differentiation) than in proliferative cells. In the rat placenta, immunohistochemical analysis showed that Gal4 is preferentially located in the maternal-fetal junctional zone. These results suggest that down-regulation of Gal4 may be involved in the promotion of trophoblast cell differentiation.

Synchronous development of Eimeria tenella in chicken caeca and utility of laser microdissection for purification of single stage schizont RNA.

Eimeria tenella is recognized worldwide as a significant pathogen in the poultry industry. However, a lack of methods for isolating developing schizonts has hindered the use of transcriptome analyses to discover novel and developmentally regulated genes. In the present study, we characterized the long-term successive development of E. tenella in infected chicken caeca and assessed the utility of laser microdissection (LMD) for the isolation of schizont RNA. Developmental stages, including those of the first, second, and third-generation schizonts and gametocytes, were synchronous. Using LMD, only the mature second-generation schizonts were successfully excised from the lamina propria, and non-degraded RNA was purified from the schizonts. E. tenella-specific genes were amplified by reverse transcription polymerase chain reaction (RT-PCR). These results augment our understanding of the E. tenella life cycle, and reveal LMD as a potentially useful tool for gene expression analyses of the intracellular stages of E. tenella.

A case of Goodpasture syndrome positive for anti-GBM antibody and MPO-ANCA complicated by a variety of serious infections.

A 62-year-old female was admitted to our hospital for investigation of acute progressive renal insufficiency and a systemic inflammatory reaction, despite treatment with several antibiotics. Laboratory data revealed severe renal insufficiency and positive titers for the myeloperoxidase anti-neutrophil cytoplasmic and anti-glomerular basement membrane antibodies. The deterioration of her general status did not allow us to perform the renal biopsy. Although corticosteroid therapy, hemodialysis, and plasma exchange were concomitantly initiated, pulmonary hemorrhage occurred several days after admission. Mechanical ventilation support was provided and continuous hemodiafiltration was carried out, following which the respiratory failure improved immediately. However, she developed clinical depression and suicidal behavior under the intensive therapy. Therefore, plasma exchange was discontinued and corticosteroid was tapered as quickly as possible. Four months after admission, platelet transfusion and short-term mechanical ventilation support improved the pulmonary hemorrhage; however, her mental status deteriorated despite psychiatric consultation and treatment with a tranquilizer. Thereafter, severe and serious systemic infection due to various pathogens including Staphylococcus aureus, Cytomegalovirus, Pneumocystis jiroveci, Pseudomonas aeruginosa, and Bacteroides recurred, and she died from systemic invasive aspergillosis (IA). We suspected severe immunosuppression caused by various factors, such as predonisolone administration, chronic renal failure on maintenance hemodialysis, depression, and malnutrition due to chronic inflammation and granulocytopenia as a side effect of ganciclovir. When treating rapidly progressive glomerulonephritis, immunosuppressive status should be carefully monitored regarding not only the dosage of therapeutic regimen but also the mental health status and nutrition of the patient.

Partial functional overlap of the three ras genes in mouse embryonic development.

In mammals, three ras genes, H-ras, N-ras and K-ras, encode homologous but distinct 21-kDa Ras proteins. We examined the in vivo functional relationship of the three ras genes in mouse embryonic development by investigating the phenotypes of mice deficient in one or multiple ras genes. H-ras-/- mice and N-ras-/- mice as well as a substantial proportion of H-ras-/-/N-ras-/- mice expressing only the K-ras gene were viable, while K-ras-/- mice were embryonically lethal, as have been reported previously. N-ras-/-/K-ras+/- mice died neonatally, while H-ras-/-/K-ras-/- embryos died much earlier than K-ras homozygous mutant fetuses. To further investigate the functional relationship of the ras genes in embryonic development, we introduced a human H-ras transgene into single or multiple ras mutant mice and found that the transgene rescued mice, including triple ras mutants, from embryonic lethality in association with correction of thin ventricular walls of the heart in null K-ras mutant mice. In situ hybridization revealed that the expression of the H-ras transgene on embryonic day E13.5 and E15.5 was more intense in major organs, including the heart, than those of endogenous ras genes. We therefore conclude that the functions of the ras genes are partially overlapping in mouse embryonic development.

Histamine ameliorates anti-glomerular basement membrane antibody-induced glomerulonephritis in rats.

Anti-glomerular basement membrane (anti-GBM)-induced glomerulonephritis involves T-helper type 1 (Th1) responses leading to rapid crescent formation. As many inflammatory and immune responses in general are affected by histamine, we examined the effects of histaminergic ligands on immune renal injury in the rat. Female Wistar-Kyoto rats were injected intraperitoneally with an antibody against the GBMs. Histaminergic ligands were then injected twice daily for 5 days after which renal function was assessed by proteinuria. Treatment with histamine led to significant dose-dependent reductions in proteinuria compared to the control antibody-injected group and markedly decreased the number of crescentic glomeruli and macrophage infiltration of the glomeruli. Furthermore, histamine significantly decreased the plasma concentration of interleukin-12, a Th1-type cytokine compared to the antibody-injected control animals. Dimaprit, an H(2)/H(4) agonist, mimicked the effects of histamine on proteinuria and crescent formation. Clozapine, an H(4) agonist, tended to mimic the effects of histamine, whereas an H(1), mepyramine, or an H(2) antagonist, ranitidine, did not reverse the protective effect of histamine. We suggest that histamine may alleviate renal injury in anti-GBM glomerulonephritis by suppressing the immune response.

Renal involvement in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary systemic arteriopathy presenting with migraines, mood disorders, focal neurologic deficits, recurrent ischemic attacks and dementia in young adults. The genesis of this disease relates to missense mutation of the Notch3 gene. We report here a newly identified CADASIL patient and discuss unique vascular lesions observed in the kidney. A 64-year-old female was admitted to our hospital for the investigation of proteinuria, hematuria and progressive neurological abnormalities. Her mother and brother died of cerebral infarction at a relatively young age despite a lack of apparent risk factors for arteriosclerosis. Over the past 4 months before admission, she had suffered from frequent transient ischemic attacks despite appropriate antiplatelet therapy. Blood examination revealed mild renal insufficiency and urinalysis revealed moderate protein excretion and dysmorphic hematuria. Magnetic resonance imaging of the brain revealed multiple infarcts and leukoencephalopathy. Histopathological analysis of the kidney revealed focal segmental mesangial proliferation, the loss and degeneration of arterial medial smooth muscle cells and arterial intimal thickening. Immunofluorescence analysis of glomeruli revealed IgA deposition in the mesangial area. Electron microscope analysis revealed electron-dense deposition also in the mesangial area. In addition, granular osmophilic material (GOM) was observed in the extraglomerular mesangial area and around the vascular smooth muscle cells. Genetic analysis of Notch3 revealed an R141C missense mutation and she was diagnosed with CADASIL complicated with IgA nephropathy. In immunohistological analysis, Notch3 stains were positive in vascular smooth muscle cells of the interlobular arteries and both afferent and efferent arterioles, and weak in the glomerular mesangial area. Antihypertensive treatment using angiotensin II receptor blocker and a low protein diet were initiated, and her urinary protein excretion decreased to 0.2 g/day. However, due to the progression of her neurological abnormalities, she became socially withdrawn. In CADASIL, GOM, abnormal accumulation of Notch3 ectodomain, is thought to induce the degeneration and loss of vascular smooth muscle cells and subsequent intimal thickening. Analysis of our cases provided that these morphological abnormalities were also observed in the CADASIL patient kidney.

Idiopathic nodular glomerulosclerosis: three Japanese cases and review of the literature.

Idiopathic nodular glomerulosclerosis (ING) is characterized as diffuse nodular glomerulosclerotic lesions, closely resembling Kimmelstiel-Wilson lesions without diabetic mellitus. We report here three Japanese cases of ING and discuss the previous reports. The patients were 75-, 48- and 84-year-old males with a history of long-term hypertension. Laboratory examination revealed moderate proteinuria and mild renal dysfunction. Diabetes mellitus was excluded by repeated clinical and laboratory investigations. Renal histology revealed nodular glomerulosclerosis, and both afferent and efferent arteriolosclerosis in all patients. In electron microscopy, the glomerular basement membrane was markedly thick in all patients. A low-protein diet and potent anti-hypertensive treatment using angiotensin-converting enzyme inhibitors were initiated in all patients and urinary protein excretion significantly reduced without the progression of renal dysfunction. We reviewed 42 previously reported cases and our three cases. The analysis revealed that common clinical features of ING are being male (82.2%) of relatively advanced age (mean age 61.3 years), with hypertension (82.2%), mild renal dysfunction (mean serum creatinine 2.9 mg/dl) and moderate urinary protein excretion (mean 4.05 g/day). Common histopathological findings of ING are nodular glomerulosclerosis (100%), arterio-arteriolosclerosis (91.2 and 89.7%) and glomerular basement membrane thickening (85.7%). In conclusion, ING is one of the phenotypes of arteriosclerotic renal disease without diabetes mellitus. Severe arterio-arteriolosclerosis may contribute to the progression to glomerular nodular formation in ING. The combination of renin-angiotensin system inhibition and a low protein diet can be beneficial for the reduction of urinary protein excretion.

A trypanosome species isolated from naturally infected Haemaphysalis hystricis ticks in Kagoshima Prefecture, Japan.

Common arthropod vectors for trypanosomes are flies, fleas and bugs. This study reports on an unknown trypanosome species isolated from naturally infected Haemaphysalis hystricis ticks, hereby, referred to as Trypanosoma KG1 isolate. The parasite has been successfully cultured in vitro with L929 or HEK 293T cell line as feeder cells. This trypanosome cannot survive in vitro without feeder cells. Following experimental infections of ticks, the trypomastigote-like and the epimastigote-like forms of this trypanosome could be detected by Giemsa-stained smears of the midgut and salivary glands of Ornithodoros moubata ticks which were made to feed on a culturing medium containing Trypanosoma KG1 isolate through an artificial membrane. Trypanosoma KG1 isolate could also be detected from Giemsa-stained smears of the haemolymph up to 30 days post-inoculation into the O. moubata haemocoel. Trypanosoma KG1 isolate cannot be propagated in laboratory animals including mice, rats, rabbits and sheep. A phylogenetic tree constructed with the 18S rRNA gene indicates that Trypanosoma KG1 is a member of the stercorarian trypanosomes.

Babesia parasites develop and are transmitted by the non-vector soft tick Ornithodoros moubata (Acari: Argasidae).

Ornithodoros moubata ticks were fed on blood infected with Babesia equi. However, the parasites were quickly cleared as evidenced by the disappearance of B. equi-specific ribosomal RNA from the ticks. We hypothesized that if the Babesia parasite can escape midgut-associated barriers a non-vector tick can become infected with Babesia. To test this hypothesis, B. equi parasite-infected blood from in vitro culture was injected into the haemocoel of ticks. B. equi-specific rRNA was surprisingly detected 45 days after injection even in the eggs. Babesia-free dogs were infested with O. moubata ticks that were infected by inoculation with B. gibsoni-infected red blood cells. Parasitaemia and antibody production against Bg-TRAP of B. gibsoni increased gradually. These results indicate that O. moubata may be a useful vector model for Babesia parasites and also a very important tool for studies on tick immunity against Babesia parasites and tick-Babesia interactions.

Histological analysis on adhesive molecules of renal intravascular large B cell lymphoma treated with CHOP chemotherapy and rituximab.

A 48-year-old man was admitted to our hospital for investigation of mild renal dysfunction. A blood examination revealed mild elevation of creatinine level (1.77 mg/dl). Urinary examination revealed mild protein excretion (0.54 g/day) and microhematuria; renal biopsy revealed the focal proliferation of large mononuclear cells with mitosis in glomerular capillaries. According to immunohistochemical analysis, the intravascular lymphomatous cells stained positively with anti-leukocyte common antigen (LCA: CD45) and CD20, indicating a B lymphocyte lineage. In electron microscopy, the glomerular capillary was filled with lymphoma cells and epithelial foot process fusion was noted. Immunohistochemical analysis on adhesive molecules revealed a lack of CD11a expression on lymphoma cells, but positive CD54 expression on endothelial cells. Systemic 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal uptake of isotopes. On the basis of these findings, we diagnosed intravascular diffuse large B cell lymphoma localized in the kidney. Despite treatment with rituximab and CHOP (prednisolone, doxorubicin, vincristine, cyclophosphamide) for 3 cycles at 1-month intervals, the renal dysfunction did not change. In histopathological analysis of the second biopsy, lymphoma cells disappeared, but focal segmental glomerulosclerosis and moderate interstitial fibrosis were noted. Electron microscopic findings revealed severe subendothelial edema with mesangial interposition, indicating severe endothelial damage. Epithelial foot process fusion was improved. These pathological analyses let us conclude that a lack of CD11a could be a candidate factor for prevention of the extravasation of lymphoma cells from blood vessels in our patient. We also presumed that the intraglomerular endothelial damage occurred due to chemotherapy-associated cell injury.

Fetal jaw movement affects condylar cartilage development.

Using a mouse exo utero system to examine the effects of fetal jaw movement on the development of condylar cartilage, we assessed the effects of restraint of the animals' mouths from opening, by suture, at embryonic day (E)15.5. We hypothesized that pre-natal jaw movement is an important mechanical factor in endochondral bone formation of the mandibular condyle. Condylar cartilage was reduced in size, and the bone-cartilage margin was ill-defined in the sutured group at E18.5. Volume, total number of cells, and number of 5-bromo-2'-deoxyuridine-positive cells in the mesenchymal zone were lower in the sutured group than in the non-sutured group at E16.5 and E18.5. Hypertrophic chondrocytes were larger, whereas fewer apoptotic chondrocytes and osteoclasts were observed in the hypertrophic zone in the sutured group at E18.5. Analysis of our data revealed that restricted fetal TMJ movement influences the process of endochondral bone formation of condylar cartilage.

The role of the hypothalamic nitric oxide in the pressor responses elicited by acute environmental stress in awake rats.

We quantitatively investigated the change in nitric oxide (NO) in the hypothalamic paraventricular nucleus (PVN) and its effect on cardiovascular regulation during shaker stress (SS) using brain microdialysis in awake rats. Male Wistar rats were fed either N(G)-nitro-L-arginine methyl ester (L-NAME, 0.7 g/L) or tap water for 2 weeks. Two days after implantation of an arterial catheter and guide shaft, a microdialysis probe was placed to perfuse the PVN with degassed Ringer solution at 2 microl/min in awake normotensive Wistar (CONTROL) and chronic L-NAME-treated hypertensive rats. After the rat was placed in a plastic cage set on a shaker, the blood pressure and heart rate was monitored and 10-min SS was loaded at a frequency of 200 cycles/min. Dialysate samples were analyzed by NO analyzer (based on the Griess reaction) every 10 min, and NOx (NO(2)(-) + NO(3)(-)) was measured. Plasma NOx was also measured before and after SS. Pressor responses elicited by SS were significantly greater in L-NAME-treated rats than in the CONTROL. Although NOx in the PVN dialysate were increased by SS in the CONTROL, these responses were attenuated in chronic L-NAME-treated rats. Resting plasma NOx were higher in the CONTROL than in L-NAME-treated rats. SS elicited no difference between two groups in plasma NOx. These results indicated that NO within the PVN, but not in systemic circulation, may play a role on the attenuation of the pressor responses elicited by SS. The dysfunction of NO release within the PVN may, in part, play a role in the exaggerated pressor responses in acute environmental stress.

Directional tendencies of Hebrew, Japanese, and English readers.

Consistent left-right and right-left reading habits are associated with corresponding directional tendencies in the reproduction of horizontally displayed visual stimuli. Inconsistent reading habits should therefore be associated with inconsis tent directional tendencies. This hypothesis was tested on Japanese readers whose reading habits were inconsistent by asking them to reproduce four series of 12-item horizontal stimulus arrays. The hypothesis was partially supported by the data which showed that, like Hebrew readers who also have inconsistent reading habits, the directional tendencies shown by the 68 Japanese readers were significantly weaker on some tasks that those shown by the 16 English readers whose left-right reading habits were consistent. The data were interpreted as showing that acquired reading habits may affect directionality in perception of visual stimuli.

Crystal structure of 2-hydroxyl-6-oxo-6-phenylhexa-2,4-dienoic acid (HPDA) hydrolase (BphD enzyme) from the Rhodococcus sp. strain RHA1 of the PCB degradation pathway.

2-Hydroxyl-6-oxo-6-phenylhexa-2,4-dienoic acid (HPDA) hydrolase (the BphD enzyme) hydrolyzes a ring-cleavage product of an aromatic compound generated in a biphenyl/polychlorinated biphenyl (PCB) degradation pathway of bacteria. The crystal structure of the BphD enzyme has been determined at 2.4 A resolution by the multiple isomorphous replacement method. The final refined model of the BphD enzyme yields an R-factor of 17.5 % at 2.4 A resolution with reasonable geometry. The BphD enzyme is an octameric enzyme with a 422 point-group symmetry. The subunit can be divided into core and lid domains. The active site of the enzyme is situated in the substrate-binding pocket, which is located between the two domains. The substrate-binding pocket can be divided into hydrophobic and hydrophilic regions. This feature of the pocket seems to be necessary for substrate binding, as the substrate is composed of hydrophilic and hydrophobic parts. The proposed orientation of the substrate seems to be consistent with the general catalytic mechanism of alpha/beta-hydrolases.

Characteristics of proper names and temporal memory of social news events.

Long-term memory of social news events was investigated by means of a questionnaire methodology with a large sample of participants. In Experiment 1, a total of 501 university students were asked to give proper names (i.e., persons and places) that related to a certain news event, and to estimate the date of the event. The accuracy of proper names (especially person names) was superior to that of estimated date (i.e., year). In addition, telescoping effects were found in the events that occurred more than 3 years ago, but time expansion effects emerged in the events that occurred less than 2 years ago. In Experiment 2, in which 182 students participated, the accuracy of proper names and the date estimates tended to be high on the events that participants judged to be given frequent exposure by the mass media. Based on these results, we discuss long-term memory and temporal schemata regarding social news events.

Antisense therapy of influenza.

The liposomally encapsulated and the free antisense phosphorothioate oligonucleotides (S-ODNs) with four target sites (PB1, PB2, PA, and NP) were tested for their abilities to inhibit virus-induced cytopathogenic effects by a MTT assay using MDCK cells. The liposomally encapsulated S-ODN complementary to the sites of the PB2-AUG initiation codon showed highly inhibitory effects. On the other hand, the inhibitory effect of the liposomally encapsulated S-ODN targeted to PB1 was considerably decreased in comparison with those directed to the PB2 target sites. The liposomally encapsulated antisense phosphorothioate oligonucleotides exhibited higher inhibitory activities than the free oligonucleotides, and showed sequence-specific inhibition, whereas the free antisense phosphorothioate oligonucleotides were observed to inhibit viral absorption to MDCK cells. Therefore, the antiviral effects of S-ODN-PB2-AUG and PA-AUG were examined in a mouse model of influenza virus A infection. Balb/c mice exposed to the influenza virus A (A/PR/8/34) strain at dose of 100 LD(50)s were treated i.v. with various doses (5-40 mg/kg) of liposomally (Tfx-10) encapsulated PB2-AUG or PA-AUG before virus infection and 1 and 3 days postinfection. PB2-AUG oligomer treated i.v. significantly prolonged the mean survival time in days (MDS) and increased the survival rates with a dose-dependent manner. We demonstrate the first successful in vivo antiviral activity of antisense administered i.v. in experimental respiratory tract infections induced with influenza virus A.