A remarkable new species of the flat bug genus Nesoproxius (Hemiptera, Aradidae), the first Oceanian representative with brachyptery.

A new flat bug species, Nesoproxiuskishimotoisp. nov., from the Oceanian region (Ogasawara Islands, Japan) is described. It is the first brachypterous representative in the genus Nesoproxius. The sexual dimorphism, nymph, and habitat are also described for the first time in this genus. A key to the species of Nesoproxius is also provided.

A Patient with Werner's Syndrome Who Underwent Aortic Valve Replacement through Minimally Invasive Cardiac Surgery.

Werner's syndrome (WS) is a genetic disorder presenting with premature senility. In the present study, we performed minimally invasive cardiac surgery (MICS)-aortic valve replacement (AVR) on a patient with Werner's syndrome who presented with aortic stenosis. The patient, a 49-year-old Japanese man, was brought to the emergency room with dyspnea during exercise. On echocardiography, severe aortic stenosis was found and surgery was planned. He had poorly controlled diabetes mellitus and underwent MICS-AVR to avoid the risk of sternal osteomyelitis, which resulted in a good outcome. The aortic valve had sclerotic changes and a genetic disease was suspected based on the onset of aortic stenosis at a young age, characteristic appearance, and various signs of aging. Genetic testing led to the diagnosis of WS.

A patient with Marfan's syndrome who developed an acute aortic dissection at 28 weeks of pregnancy treated with aortic root replacement.

The patient was a 31-year-old pregnant woman who gave birth to her first child by vaginal delivery 7 years ago. She was diagnosed with Marfan's syndrome based on physical findings; however, the condition was not diagnosed before the onset. The patient developed acute aortic dissection at 28 weeks of pregnancy. A cesarean section was first performed to save the patient's life; then, a total hysterectomy was performed to prevent the risk of postpartum hemorrhage. Furthermore, aortic root replacement was performed using a temporary mechanical valve. The patient and her child have survived without any complications.

Radiological findings and outcomes of anterior wall fractures in pertrochanteric fractures.

BACKGROUND: Anterior wall fractures with comminution at the anterior cortex in pertrochanteric fractures are relatively rare. We aimed to investigate the prevalence and clinical findings of anterior wall fractures in this comparative cohort study. METHODS: We reviewed 516 consecutive patients who underwent internal fixation. Anterior wall fractures were classified into three types: proximal, distal, and proximal/distal. Outcome measures included demographic data, residual anterior cortex length, fracture reduction, tip-apex distance (TAD), sliding distance, bone union, and revision surgery. We compared radiological outcomes between patients with anterior wall fractures and posterior comminuted fractures without an anterior wall fracture. The groups were matched for age and sex. RESULTS: Anterior wall fractures were noted in 44 patients (8.5%). Residual anterior cortex length was shorter for the proximal/distal type. The distal type was the most common, was the most difficult to achieve an acceptable reduction status for, and was associated with the longest sliding distance. The proportion of unacceptable reduction status was higher for anterior wall fractures. However, there were no statistically significant differences between anterior wall fractures and posterior comminuted fractures without an anterior wall fracture in terms of TAD, sliding distance, bone union, and revision rate. CONCLUSIONS: This study suggests that anterior wall fracture is not a significant predictor of over-sliding distance.

Clinical outcomes of treatment with locking compression plates for distal femoral fractures in a retrospective cohort.

BACKGROUND: Plate fixation is one of the standard surgical treatments for distal femoral fractures. There are few reports on the relationship between the screw position and bone union when fixing by the bridging plate (relative stability) method. METHODS: This retrospective study included 71 distal femoral fractures of 70 patients who were treated with the locking compression plate for distal femur (DePuy Synthes Co., Ltd, New Brunswick, CA, USA). The following measurements were evaluated and analyzed: (1) bone union rate, (2) bridge span length (distance between screws across the fracture), (3) plate span ratio (plate length/bone fracture length), (4) number of empty holes (number of screw holes not inserted around the fracture), and (5) medial fracture distance (bone fracture distance on the medial side of the distal femur). Patient demographics (age), comorbidities (smoking, diabetes, chronic steroid use, dialysis), and injury characteristics (AO type, open fracture, infection) were obtained for all participants. Univariate analysis was performed on them. RESULTS: Of 71 fractures, 26 fractures were simple fractures, 45 fractures were comminuted fractures, and 7 fractures resulted in non-union. Non-union rate was significantly higher in comminuted fractures with bone medial fracture distance exceeding 5 mm. Non-union was founded in simple fractures with bone medial fracture distance exceeding 2 mm, but not significant (p = 0.06). In cases with simple fractures, one non-union case had one empty hole and one non-union case had four empty holes, whereas in cases with comminuted fractures, five non-union cases had two more empty holes. CONCLUSIONS: We concluded that bone fragment distance between fracture fragments is more important than bridge span length of the fracture site and the number of empty holes. Smoking and medial fracture distance are prognostic risk factors of nonunion in distal femoral fractures treated with LCP as bridging plate.

Effectiveness on high-grade cervical abnormalities and long-term safety of the quadrivalent human papillomavirus vaccine in Japanese women.

This study for the first time assessed quadrivalent human papillomavirus (qHPV) vaccine effectiveness against HPV6/11/16/18-related high-grade cervical disease in Japanese women (16-26 years old), as previously demonstrated in overseas trials, and vaccine safety in a longer term (48-month) open-label study (NCT01544478). Participants received three doses of qHPV vaccine (Day 1, Month 2, Month 6). Effectiveness endpoints, assessed in the per-protocol population, included incidence of HPV6/11/16/18-related cervical intraepithelial neoplasia (CIN) Grade 2 or worse (CIN Grade 2 and 3, adenocarcinoma in situ, and/or cervical cancer) as primary endpoint and incidence of external genital lesions (EGLs). Disease related to other high-risk HPV types was also assessed. Adverse events (AEs) and serious AEs (SAEs) were collected from Days 1-15 after any vaccination; vaccine-related SAEs, deaths, and new medical conditions were collected throughout the study. A total of 1030 women received at least one vaccination. No cases of CIN2 or worse or EGLs were reported in the per-protocol population. Injection site-related AEs were reported in 14.5% of participants; most were mild and resolved within 15 days. Vaccine-related systemic AEs occurred in 8.6% of participants, most commonly headache (2.3%), malaise (1.7%), and pyrexia (1.3%). There were no vaccine-related SAEs; one participant discontinued due to a vaccine-related AE of mild uticaria. Overall, qHPV vaccine effectiveness against HPV6/11/16/18-related high-grade cervical disease and EGLs was indicated in Japanese women. The vaccine was well-tolerated, without new safety signals throughout the 48-month study period. Findings are consistent with overseas qHPV vaccine pivotal trials. CLINICAL TRIAL REGISTRY: clinicaltrials.gov; NCT01544478.

Involvement of transient receptor potential melastatin 4 channels in the resting membrane potential setting and cholinergic contractile responses in mouse detrusor and ileal smooth muscles.

Here, we investigated the effects of 9-hydroxyphenanthrene (9-phenanthrol), a potent and selective transient receptor potential melastatin 4 (TRPM4) channel blocker, on the resting membrane potential and cholinergic contractile responses to elucidate the functional role of TRPM4 channels in the contractile activities of mouse detrusor and ileal longitudinal smooth muscles. We observed that, 9-phenanthrol (3-30 µM) did not significantly inhibit high K+-induced contractions in both preparations; however, 9-phenanthrol (10 µM) strongly inhibited cholinergic contractions evoked by electrical field stimulation in detrusor preparations compared to inhibitions in ileal preparations. 9-Phenanthrol (10 µM) significantly inhibited the muscarinic agonist, carbachol-induced contractile responses and slowed the maximum upstroke velocities of the contraction in detrusor preparations. However, the agent (10 µM) did not inhibit the contractions due to intracellular Ca2+ release evoked by carbachol, suggesting that the inhibitory effect of 9-phenanthrol may primarily be due to the inhibition of the membrane depolarization process incurred by TRPM4 channels. On the other hand, 9-phenanthrol (10 µM) did not affect carbachol-induced contractile responses in ileal preparations. Further, 9-phenanthrol (10 µM) significantly hyperpolarized the resting membrane potential and decreased the basal tone in both detrusor and ileal muscle preparations. Taken together, our results suggest that TRPM4 channels are constitutively active and are involved in setting of the resting membrane potential, thereby regulating the basal tone in detrusor and ileal smooth muscles. Thus, TRPM4 channels play a significant role in cholinergic signaling in detrusor, but not ileal, smooth muscles.

Possible antagonistic effects of the TRPC4 channel blocker ML204 on M2 and M3 muscarinic receptors in mouse ileal and detrusor smooth muscles and atrial myocardium.

ML204, a potent transient receptor potential canonical 4 (TRPC4) channel blocker, is often used to elucidate the involvement of TRPC4 channels in receptor-operated signaling processes in visceral smooth muscles. In the present study, we investigated the possible antagonistic actions of ML204 on M2 and M3 muscarinic receptors, which mediate contractions in mouse ileal and detrusor smooth muscles. In ileal and detrusor smooth muscle preparations, ML204 (3 or 10 µM) significantly inhibited electrical field stimulation (EFS)-evoked cholinergic contractions. However, it did not significantly inhibit high K+-induced and EFS-evoked non-cholinergic contractions in the ileal preparations. When the muscarinic agonist, carbachol was cumulatively applied, ML204 (1, 3 and 10 µM) caused a rightward parallel shift of the concentration-response curves of carbachol. Additionally, ML204 (1, 3 and 10 µM) inhibited carbachol-induced negative chronotropic response in atrial preparations, which is mediated by M2 muscarinic receptors. Furthermore, ML204 significantly inhibited the contractions evoked by carbachol-induced intracellular Ca2+ release, which is mediated by M3 muscarinic receptors. These results suggested that ML204 might exhibit antagonistic actions on M2 and M3 muscarinic receptors; in addition, the inhibitory effects of ML204 against EFS-induced cholinergic contractions might be attributed to this receptor antagonism rather than inhibition of TRPC4 channel activity. Therefore, these effects should be considered when ML204 is used as a TRPC4 channel blocker.

Muscarinic M2 receptor promotes vasopressin synthesis in mice supraoptic nuclei.

Muscarinic acetylcholine receptors have been suggested to be implicated in arginine-vasopressin secretion because intracerebroventricular muscarinic agonist administration induces arginine-vasopressin release into the circulation. Although which subtype is involved in the regulation of arginine-vasopressin secretion is unclear, M2 receptors have been reported to be highly expressed in the hypothalamus. In the present study, M2 receptor-knockout mice were used to elucidate whether M2 receptor regulates arginine-vasopressin synthesis in the paraventricular nuclei and supraoptic nuclei of the hypothalamus. The number of arginine-vasopressin-immunoreactive neurons in M2 receptor-knockout mice was significantly decreased in the supraoptic nuclei, but not in the paraventricular nuclei compared with wild-type mice. Plasma arginine-vasopressin level in M2 receptor-knockout mice was also significantly lower than in the wild-type mice. Urinary volume and frequency as well as water intake in M2 receptor-knockout mice were significantly higher than those in wild-type mice. The V2 vasopressin receptor expression in kidneys of M2 receptor-knockout mice was comparable with that of wild-type mice, and increased urination in M2 receptor-knockout mice was significantly decreased by administration of desmopressin, a specific V2 receptor agonist, suggesting that V2 receptors in the kidneys of M2 receptor-knockout mice are intact. These results suggest that M2 receptors promote arginine-vasopressin synthesis in the supraoptic nuclei and play a role in the regulation and maintenance of body fluid.

Our Experience with 131 Cases of Simultaneous Breast Implant Exhange with Fat (SIEF).

BACKGROUND: Breast augmentation with fat injection is a growing trend in Japan. Many Japanese patients experiencing breast implant complications are requesting to have their breast implants removed and simultaneously exchanged with autologous fat injection. The keys of our simultaneous implant exchange with fat (SIEF) process are to embrace the "Coleman technique" and to carefully detach implant capsules when removing breast implants. Furthermore, we carefully inject fat to avoid necrosis. METHODS: Between January 2010 and January 2015, we investigated consecutively 131 Japanese patients whom we could follow up for over 6 months postsurgery. We ascertained the usefulness of SIEF by assessing changes in breast size, complications, and a satisfaction survey. RESULTS: There were no serious complications. We had experienced mild complications in 9.2% of patients (12/131). Partial fat necrosis with inflammation occurred in 2.3% of patients (3/131), seroma in the capsule in 3.1% (4/131), complaints of nodules (cysts, lumps) in 3.1% (4/131), and 1 hematoma patient (0.8%). At 6 months after surgery (n = 131), breast cup size (by Japanese Industrial Standards) had decreased by less than 1 cup size, despite SIEF. At 6 months, we performed a postsurgery satisfaction survey, and only 4% of the patients (5/131) were not satisfied with their surgery results. CONCLUSIONS: SIEF is a very safe and effective procedure. Breast implants removed with a low invasive traumatic approach and centrifuged fat injected with the "Coleman technique" are important principles in our practice. Furthermore, avoiding fat necrosis is one of the most important considerations, and our SIEF approach allows us to better control this potential complication during the surgical process.

Inhibitory effects of SKF96365 on the activities of K(+) channels in mouse small intestinal smooth muscle cells.

In order to investigate the effects of SKF96365 (SKF), which is a non-selective cationic channel blocker, on K(+) channel currents, we recorded currents through ATP sensitive K(+) (IKATP), voltage-gated K(+) (IKv) and Ca(2+) activated K(+) channels (IBK) in the absence and presence of SKF in single small intestinal myocytes of mice with patch-clamp techniques. SKF (10 µM) reversibly abolished IKATP that was induced by cromakalim (10 µM), which is a selective ATP sensitive K(+) channel opener. These inhibitory effects were induced in a concentration-dependent and voltage-independent manner. The 50% inhibitory concentration (IC50) was 0.85 µM, which was obviously lower than that reported for the muscarinic cationic current. In addition, SKF (1 µM ≈ the IC50 value in IKATP suppression) reversibly inhibited the IKv that was induced by repetitive depolarizing pulses from -80 to 20 mV. However, the extent of the inhibitory effects was only ~30%. In contrast, SKF (1 µM) had no significant effects on spontaneous transient IBK and caffeine-induced IBK. These results indicated that SKF inhibited ATP sensitive K(+) channels and voltage-gated K(+) channels, with the ATP sensitive K(+) channels being more sensitive than the voltage-gated K(+) channels. These inhibitory effects on K(+) channels should be considered when SKF is used as a cationic channel blocker.

Endoloop ligation technique for prolapsed pedunculated submucous uterine myoma: utility and reliability.

PURPOSE: We use a non-surgical endoloop snare technique to remove prolapsed pedunculated submucous uterine myomas under the concept that ligating the pedicle causes tumor necrosis and natural elimination of the tumor. We evaluated our method on the basis of clinical outcomes. METHODS: For pertinent clinical data, we reviewed the hospital records of 11 patients treated by our new method between July 2009 and 2010 and followed up for 22-31 months. RESULTS: Patients' mean age was 40.9 years, and the mean hemoglobin level was 10.6 g/dl. None required urgent hospitalization, blood transfusion, or laparotomy. The tumors were eliminated naturally or removed by cutting necrotic pedicle within 4-11 days. One patient required a second endoloop application. Another one patient required follow-up surgery for a second submucous myoma, adenomyosis, and persistent hypermenorrhea. CONCLUSIONS: Endoloop ligation is feasible for eliminating prolapsed pedunculated submucous myoma. It is simple and safe and can be performed in the outpatient setting.

Transmission of the major skin microbiota, Malassezia, from mother to neonate.

BACKGROUND: Skin surface colonization starts after birth. It is thought that early microbial colonization affects the development of skin immune functions. Although Malassezia is the predominant fungus in the skin microbiota in healthy individuals, the microorganism is associated with atopic dermatitis and seborrheic dermatitis. In the present study, transmission of skin microbiota from mothers to their neonates was elucidated using the Malassezia microbiota as an indicator. METHODS: Temporal changes in the level of Malassezia colonization of the skin from 27 neonates and mothers were investigated by real-time polymerase chain reaction assay. The genotypes of Malassezia colonizing the neonate and mother were also determined. RESULTS: Malassezia was detected from 89% and 100% of neonate samples on days 0 and 1 after birth, respectively. Subsequently, the level of Malassezia colonization of the neonates increased with time, whereas that of the mothers did not change. The Malassezia diversity of neonates shifted to the adult type by day 30. The genotype of Malassezia colonizing the skin of neonates agreed well with that of Malassezia colonizing the skin of the mothers. CONCLUSION: Fungal microbiota colonization of neonates began on day 0, and the fungal microbiota of neonates had changed to the adult type by day 30. To our knowledge, this is the first report of a molecular analysis of the fungal microbiota of neonates.

Clinical outcomes and hemodynamics of the 19-mm Perimount Magna bioprosthesis in an aortic position: comparison with the 19-mm Medtronic Mosaic Ultra Valve.

BACKGROUND: When aortic valve replacement is performed in patients with a small aortic annulus, prosthesis-patient mismatch (PPM) is of concern because it can affect postoperative clinical outcomes. Although larger bioprosthetic valves have been well studied, the hemodynamics of 19-mm bioprostheses have been reported in only a small number of patients. The effectiveness as well as the impact of PPM on outcomes are thus still unclear. METHODS AND RESULTS: Postoperative clinical and hemodynamic variables were compared in 67 patients with a 19-mm Carpentier Edwards Perimount Magna bioprosthesis and in 10 patients with a 19-mm Medtronic Mosaic Ultra valve. Mean follow-up time was 13 months. There was no in-hospital mortality. Echocardiography 6.5±4.0 months after surgery showed significant decreases in the mean left ventricular (LV)-aortic pressure gradient, and decreases in the mean LV mass index. Reduction in LV mass index did not differ between the valve groups, despite a higher pressure gradient in the Mosaic group. Although PPM was detected in 21 patients in the Magna group, it did not affect regression of the LV mass index during the follow-up period. CONCLUSIONS: Use of the 19-mm Magna bioprosthesis appears to provide satisfactory clinical results. LV-aortic pressure gradient was lower in the Magna group. The present data suggest that PPM is not related to reduction in the LV mass index.

Mid-term outcomes after aortic valve replacement with the 17-mm St. Jude Medical Regent valve.

BACKGROUND: When aortic valve replacement (AVR) is performed in patients with a small aortic annulus, prosthesis-patient mismatch (PPM) is of concern. We investigated the mid-term outcomes of AVR with a 17-mm mechanical prosthesis. METHODS AND RESULTS: Seventy-eight patients with aortic stenosis underwent AVR with a 17-mm St. Jude Medical Regent prosthesis. Echocardiography was performed preoperatively, at discharge, and at follow-up (mean follow-up, 33 months). Patients were divided into 2 groups: with and without PPM at discharge. Between-group differences in postoperative variables, particularly survival, were analyzed. Overall hospital mortality was 2.6%. Actuarial 1- and 5-year survival rates were 95% and 79%, respectively. Diabetes and renal insufficiency were associated with long-term mortality. Freedom from major adverse valve-related cardiac events at 1 year and 5 years was 97.3% and 93.9%, respectively. Diabetes was shown to be an independent risk factor for major adverse valve-related cardiac events. Echocardiography 13 months after AVR showed a significant increase in mean effective orifice area index, decrease in mean left ventricular-aortic pressure gradient, and decrease in mean left ventricular mass index. PPM at discharge did not influence long-term survival or left ventricular mass regression. CONCLUSIONS: The 17-mm Regent prosthesis provided satisfactory clinical and hemodynamic results. It is a reliable choice for patients with a small aortic annulus.

A pilot study on ultrasound-assisted liposuction of the greater omentum in porcine models.

The greater omentum is the largest depot of visceral fat, and recent studies implicate removal of omental fat as a therapeutic option for metabolic syndrome (MS). This study evaluated the technical feasibility of reducing omental fat by using ultrasound-assisted liposuction (UAL) in porcine models. We removed as much omental adipose tissues as possible with a novel ultrasonic aspirator specifically designed for visceral liposuction that was inserted into the peritoneal cavity via the bilateral hypochondrial trocars. The greater part of the omental surface was emulsified and suctioned within 12.4 ± 9.2 (mean ± SD) min. In the survival study, all animals survived for two weeks without clinically evident complications following UAL. Histological examinations confirmed a substantial reduction in omental fat in pigs subjected to UAL. In conclusion, the pilot animal study conducted here demonstrated the technical feasibility of omental liposuction. UAL thus has potential as a relatively non-invasive liposuction approach to treat MS by selectively reducing the visceral fat content of the greater omentum.

Surgical treatment for thoracic aneurysms: comparison of stent grafting and open surgery.

OBJECTIVES: Early and mid-term results of stent graft (SG) treatment for thoracic aortic aneurysms (thoracic endovascular aneurysm repair: TEVAR) were retrospectively compared with open surgical treatment. METHODS: The records of 213 patients in whom single thoracic aortic aneurysm repairs had been performed in our department from January 2006 through August 31, 2009 were reviewed. Acute aortic dissection was excluded. Each case was reviewed for indications for TEVAR from an anatomical standpoint. Among 62 cases in which TEVAR was indicated, 30 (SG group) were treated by TEVAR and 32, by open surgery (OP group). Early and mid-term results were analyzed retrospectively in both groups. RESULTS: There were no operative deaths in either group. The SG group demonstrated significantly less operative bleeding, a shorter operative time, and shorter postoperative hospital stay compared with the OP group. There were 3 deaths in the SG group and 4 in the OP group, which occurred within an average of 656.4 days during the follow up period. The 3 year actuarial survival rate was 88.7% in the SG group and 87.1% in the OP group, and there were no significant differences between the groups. CONCLUSION: Although early and mid-term results of TEVAR and open surgery were similar, TEVAR is generally less invasive and may be preferable for high-risk patients, compared with open surgical repair. (English Translation of Jpn J Vasc Surg 2010; 19: 51-56.).

Clinical experience with a new vascular graft free from biodegradable material.

Triplex (Terumo Co., Tokyo, Japan), a newly developed large diameter vascular graft sealed with a non-biodegradable material, is expected to reduce inflammatory reaction. We confirmed its safe implantation and assessed inflammatory reaction after thoracic aortic surgery. Between January 2009 and February 2010, 101 consecutive patients underwent thoracic aortic replacement. Triplex grafts were implanted in 40 patients, and bovine-collagen coated grafts (Hemashield, Boston Scientific, Boston, MA, USA) were implanted in 61 patients. During the postoperative course, body temperature and laboratory findings including inflammatory markers were examined. The mean operation time and amount of bleeding during operation were equivalent in the two groups. The mean body temperature and C-reactive protein in patients implanted with Triplex were significantly lower than those in patients implanted with Hemashield grafts. The mean white blood cell count tended to be at lower levels in patients implanted with Triplex grafts. No patients in both groups suffered postoperative complications associated with the prosthetic grafts. Triplex was confirmed to be safely applied for thoracic aortic surgery as well as the conventional vascular grafts and to reduce postoperative inflammatory reaction.

[A case of duodenal gangliocytic paraganglioma with lymph node metastasis].

A 28-year-old man complained of tarry stool. A series of examinations showed a submucosal tumor with bleeding at the papilla of Vater and a swollen # 17b lymph node, both of which indicated a hypervascular tumor. The pathological findings of the enucleated tumor specimens revealed gangliocytic paraganglioma with metastasis to the # 17b lymph node. Additional pancreaticoduodenectomy revealed another # 17b lymph node metastasis 7-mm in diameter. Although the majority of gangliocytic paragangliomas are benign, 7% of reported cases have lymph node metastases, as shown in the present case. These findings are important in treating patients with gangliocytic paraganglioma.

Kallidinogenase normalizes retinal vasopermeability in streptozotocin-induced diabetic rats: potential roles of vascular endothelial growth factor and nitric oxide.

We studied the suppressant effect of kallidinogenase on retinal vascular permeability and vascular endothelial growth factor (VEGF) in diabetic rats. Diabetes was induced by intravenously injecting streptozotocin (60 mg/kg body weight) dissolved in citrate buffer. Kallidinogenase (7 microg/kg/day) was injected intravenously once daily for 21 days. The retinal vascular permeability was estimated from the amount of fluorescent dye leaking into the retina after administration of fluorescein isothiocyanate-conjugated dextran. VEGF in intraocular fluids was quantified by an enzyme-linked immunosorbent assay. The amounts of nitrite and nitrate in the retina were quantified by a fluorescence method using 2,3-diaminonaphthalene. Retinal vascular permeability in the diabetic control group was about 5.5 times higher than in the normal control group (P<0.001). Kallidinogenase suppressed the increased retinal vascular permeability. In the diabetic control group, the VEGF level was three times that of the normal control group (diabetic control group, 160+/-12 pg/ml; normal control group, 54+/-9 pg/ml; P<0.001). The VEGF concentration in the kallidinogenase-treated group was 120+/-12 pg/ml (P<0.05). In the diabetic control group, the amounts of nitrite and nitrate in the retina were lower by about 2.6-fold, compared with the normal control group (P<0.05). Kallidinogenase almost normalized the decreases in nitrite and nitrate in the retina. The current study showed beneficial effects of kallidinogenase on increased retinal vascular permeability and VEGF in diabetic rats, suggesting that kallidinogenase may be effective for simple retinopathy in patients with diabetes.