Search

The zona pellucida (ZP) protein constitutes the egg envelope, which surrounds the vertebrate embryo. We performed a comprehensive study on the molecular evolution of ZP genes in Teleostei by cloning and analyzing the expression of ZP genes in fish of Anguilliformes in Elopomorpha, Osteoglossiformes in Osteoglossomorpha, and Clupeiformes in Otocephala to cover unsurveyed fish groups in Teleostei. The present results confirmed findings from our previous reports that the principal organ of ZP gene expression changed from ovary to liver in the common ancestors of Clupeocephala. Even fish species that synthesize egg envelopes in the liver carry the ovary-expressed ZP proteins as minor egg envelope components that were produced by gene duplication during the early stage of Teleostei evolution. The amino acid repeat sequences located at the N-terminal region of ZP proteins are known to be the substrates of transglutaminase responsible for egg envelope hardening and hatching. A repeat sequence was found in zona pellucida Cs of phylogenetically early diverged fish. After changing the synthesis organ, its role is inherited by the N-terminal Pro-Gln-Xaa repeat sequence in liver-expressed zona pellucida B genes of Clupeocephala. These results suggest that teleost ZP genes have independently evolved to maintain fish-specific functions, such as egg envelope hardening and egg envelope digestion, at hatching., (© 2022 Wiley Periodicals LLC.)

Objectives: To investigate long-term chronological changes in functional renal volume and renal function after nephron-sparing surgery, and factors that contribute to the progression of postoperative chronic kidney disease., Methods: A total of 80 patients who underwent nephron-sparing surgery were enrolled in this prospective observational study. The renal function deterioration group was defined as patients whose estimated glomerular filtration rate at 5 postoperative years decreased by ≥20% relative to that before surgery., Results: The predicted estimated glomerular filtration rate, calculated based on the functional renal volume at 5 postoperative years, was strongly correlated with the postoperative estimated glomerular filtration rate (Spearman's ρ = 0.89, P < 0.001). The rate of new-onset stage IIIb chronic kidney disease was significantly higher in the renal function deterioration group than in the stable renal function group (P < 0.001). Multivariate analysis identified proteinuria (P = 0.017), small preoperative total functional renal volume (≤250 mL, P = 0.046) and large tumor volume (≥4.5 mL, P = 0.036) as independent factors associated with renal function deterioration., Conclusions: Our findings show that the functional renal volume is significantly associated with renal function, even in the long-term postoperative period. Additionally, for patients with preoperative proteinuria, large tumor volume and small total preoperative functional renal volume, both oncological follow ups and medical interventions, including prevention of lifestyle-related diseases, might prevent the progression of chronic kidney disease., (© 2021 The Japanese Urological Association.)

Purpose: The change in functional renal volume (FRV) has an absolute influence on renal function after nephrectomy (Nx) or nephron-sparing surgery (NSS). In this study, we prospectively examined whether the postoperative renal function following Nx and NSS could be accurately predicted and assessed the reproducibility of our newly developed 3-D image reconstruction system (Kashihara) to measure the FRV., Methods: We enrolled 98 patients who underwent Nx and 41 patients who underwent NSS from April 2006 to September 2009 to predict postoperative FRV and renal function. FRV was measured before and after (1 month and 1 year) renal surgery. The postoperative estimated glomerular filtration rate (eGFR) was predicted from the preoperative eGFR calculated from the serum creatinine (sCr) level and the ratio of the postoperative/preoperative FRV. To assess the reproducibility and accuracy of our newly developed 3-dimensional (3-D) image reconstruction system, FRV was measured by five examiners using images obtained by CT (five cases) and MRI (five cases)., Results: Significant correlation was found both for FRV and for renal function between the predictive values and the actually measured values at 1 month and 1 year after surgery, not only in the Nx group, but also in the NSS group. The accuracy and reproducibility could be confirmed both with CT and MRI studies., Conclusions: The postoperative FRV and renal function could be predicted preoperatively using a 3-D image reconstructive system, preoperative routine diagnostic imaging, and preoperative sCr level.

Background: To evaluate the clinical usefulness of estimated glomerular filtration rate (eGFR) divided by functional renal volume (FRV) measured by three-dimensional image reconstruction (eGFR/FRV) for the prediction of functional outcomes after nephrectomy., Methods: Eighty-three patients who underwent nephrectomy were enrolled. The FRV of each patient was measured before surgery. Preoperative medical information on proteinuria, blood pressure, blood glucose level, body mass index (BMI), hemoglobin level and serum cholesterol level were also obtained. We evaluated the relationships between eGFR/FRV and each of these parameters before surgery. We also assessed the potential relationship between eGFR/FRV and the 3-year postoperative eGFR. Stepwise multiple regression analyses were conducted to elucidate independent factors., Results: The median FRV and eGFR were 310.15 cm3 and 79.0 ml/min/1.73 m² before surgery, respectively. The correlation between FRV and eGFR was statistically significant (r = 0.465, P < 0.001). The median eGFR/FRV was 0.24 ml/min/1.73 m²/cm³. Stepwise multiple regression analysis showed that the independent parameters (multiple correlation coefficient, r = 0.389, P = 0.031) associated with eGFR/FRV were proteinuria, BMI, age and hypertension. Proteinuria was statistically associated with eGFR/FRV, and the independent parameters (multiple correlation coefficient, r = 0.694, P < 0.001) associated with the 3-year postoperative eGFR were age, BMI and eGFR/FRV. The eGFR/FRV was statistically associated with the 3-year postoperative eGFR (r = 0.559, P < 0.001)., Conclusion: The present results demonstrated that patients with proteinuria are expected to have a lower eGFR/FRV than those without proteinuria. The present study also supports the notion that eGFR/FRV is the primary determinant of the long-term functional outcome after nephrectomy. It should be taken into consideration that patients with a low eGFR/FRV may develop chronic kidney disease after nephrectomy.

The aim of this study was to investigate risk factors affecting 5- and 10-year survival in autotransplantation of third molars with complete root formation at dental clinics. Participating dentists were requested to provide information on transplantations performed between 1 January 1990 and 31 December 2009. After data screening and elimination, 183 teeth in 171 men aged 20-72 years (mean, 44.8 years) and 205 teeth in 189 women aged 20-74 years (mean, 42.0 years) were included in the study. A single-factor analysis using the log-rank test revealed that the following factors had a significant influence (p<0.05) on 5-year survival in transplanted teeth in men: recipient site in the maxilla and fewer than 25 present teeth; those for 10-year survival, on the other hand, were recipient site tooth extraction due to periodontal disease, recipient site in the maxilla, fewer than 25 present teeth, and Eichner index Group B1 to C. Cox regression analysis revealed that the odds ratio for 5-year survival for recipient site in the maxilla was 2.873 (95% CI, 1.073-7.695), while that for 10-year survival was 3.713 (95% CI, 1.601-8.609) for recipient site extraction due to periodontal disease, 2.190 (95% CI, 1.021-4.700) for recipient site in the maxilla, and 3.110 (95% CI, 1.470-6.581) for fewer than 25 present teeth. In women, the log-rank test indicated experience of less than 10-year in performing treatment as a significant factor (p <0.05) in 5-year survival. These results suggest that medium-term survival in transplanted teeth is influenced by operational risk factors in women, while long-term survival in transplanted teeth is influenced by individual oral status in men.

Gender-related risk factors in the survival of transplanted teeth with complete root formation have not yet been identified. The purpose of this study was to investigate gender differences in tooth autotransplantation at dental clinics. We asked participating dentists to provide information on transplantations they had undertaken from 1 January 1990 to 1931 December 2010. The data were screened to exclude patients who underwent more than one transplantation, smokers or those whose smoking habits were unknown, patients under 30 or who were 70 years old and over, cases where the transplanted teeth had incomplete root formation or multiple roots and those with fewer than 20 present teeth post-operation. We analysed 73 teeth of 73 males (mean age, 47.2 years) and 106 teeth of 106 females (mean age, 45.3 years) in this study. The cumulative survival rate and mean survival time were calculated using the Kaplan-Meier method. The cumulative survival rate for males was 88.3% at the 5-year mark, 64.8% at 10 years and 48.6% at 15 years; for females, it was 97.2% at the 5-year mark, 85.9% at 10 years and 85.9% at 15 years. A log-rank test indicated the difference between males and females to be significant (P = 0.011). There was also a significant difference in the main causes for the loss of transplanted teeth: males lost more transplanted teeth due to attachment loss than females (P < 0.05). These results indicate that males require more attention during the autotransplantation process, particularly at the stage of pre-operation evaluation and that of follow-up maintenance., (© 2013 Blackwell Publishing Ltd.)

The aim of this study was to investigate risk factors with age in the long-term prognosis of autotransplantation of teeth with complete root formation at dental clinics. Participating dentists were asked to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. The data were screened to exclude patients who were under 25 or 70 years of age and over, those who were smokers or whose smoking habits were unknown, those whose transplanted teeth had incomplete root formation or multiple roots and those with fewer than 25 present teeth post-operation. The participants in this study were 71 men (74 teeth) and 100 women (107 teeth) ranging from 25 to 69 years of age. Third molars were used as donor teeth in 89·0% of the cases. The participants were divided into three age groups of 25-39, 40-54 and 55-69. Survival analysis was conducted using the Kaplan-Meier method, and a log-rank test revealed that there were no significant differences in age groups for men or women. Cox regression analysis indicated that the survival of transplanted teeth was not influenced by age. However, although not statistically significant, the clinical success rate was lower in the 55-69-year-old group than that in the younger groups. These results indicate that if suitable donor teeth are available and the conditions are right, autotransplantation is a viable treatment for missing teeth regardless of the age of the patient., (© 2012 Blackwell Publishing Ltd.)

The purpose of this study was to analyze the survival rate in autotransplanted premolars with complete root formation in dental clinics. Participating dentists were requested to provide information on transplantations they had undertaken between 1 January 1990 and 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. Data for other tooth types and for teeth with incomplete root formation were eliminated. In this study, data on 40 teeth in 35 patients were analyzed. Participants consisted of 17 men and 18 women ranging from 24 to 79 years in age (mean age, 43.7 years). The cumulative survival rate was 100% at the 5-year mark and 72.7% at 10 years, as calculated by the Kaplan-Meier method. Single-factor analysis revealed that "transplanted to the molar regions" was a significant risk factor (p<0.05) influencing the survival of transplanted teeth. However, a Cox regression analysis showed no significance. The results of this study suggest that, in cases where there is a suitable donor tooth and the oral condition is good, premolar autotransplantation is a viable treatment option, even when there is complete root formation in the donor teeth.

The aim of this study was to compare the prognosis of separated and non-separated tooth autotransplantation of the upper first and second molars with complete root formation undertaken at dental clinics. The participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. This study analysed 35 separated teeth and 22 non-separated teeth of 47 participants ranging from 27 to 76 years of age (mean age: 55·0 years) after data screening and elimination. The cumulative post-transplantation survival rate at 10 years was 77·1% for separated teeth and 63·6% for non-separated teeth as calculated with the Kaplan-Meier method. There were no significant differences between separated teeth and non-separated teeth in a log rank test (P = 0·687). Separated-tooth autotransplantation can help fill narrow recipient sites and increase occlusal supporting zones, but the clinical success rate was only 48·6%. Although transplantation of teeth with complete root formation has limited prognosis, transplantation of upper first and second molars, whether separated or non-separated, is a viable option to replace missing teeth., (© 2012 Blackwell Publishing Ltd.)

The main reasons for loss of autotransplanted teeth are different from those involved in natural teeth loss. The aim of this study was to investigate which procedures were employed to treat spaces vacated when autotransplanted teeth were lost. Participating dentists were requested to provide information on transplantations they had undertaken. A total of 614 teeth in 552 patients (37 dentists) ranging in age from 17 to 79 years (mean age: 44.1 years) were examined. A total of 102 transplanted teeth were lost during the observation period. Procedures for treatment of spaces vacated were not influenced by main reason for transplanted tooth loss. The procedure used to treat depended on the original prosthodontic treatment of the transplanted teeth. For single crowns, the spaces were left empty (33.9%) or replaced by bridge work (30.5%), implants (20.3%), or dentures (10.2%). For single crowns in the upper and lower second molar regions, the spaces were usually left empty (upper 100%, lower 71.4%), while for those in the upper and lower first molar regions, the spaces were often replaced by bridge work (upper 41.7%, lower 50.0%). For bridge abutments, spaces were replaced by dentures (42.9%), implants (33.3%), or left empty (14.3%), and in the lower second molar region, they were mostly replaced by implants (5 cases, 41.7%). For most denture abutment cases, the spaces were replaced by dentures (88.9%). During the survival period of the transplanted teeth, the masticatory burden on the other teeth is reduced and the adjacent teeth are supported by the transplanted tooth. Even if transplanted teeth are eventually lost, traditional procedures can be performed to fill the vacated space.

The aim of this study was to investigate the risk factors affecting long-term prognosis of autotransplantation of third molars with complete root formation in males at dental clinics. Participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. After data screening and elimination, participants of this study consisted of 183 teeth of 171 males ranging from 20 to 72 years of age (mean age, 44·8 years). The cumulative survival rate was 86·0% at the 5-year mark, 59·1% at 10 years and 28·0% at 15 years. The mean survival time was 134·5 months, as calculated by the Kaplan-Meier method. Single factor analysis using the log-rank test showed that the following factors had significant influence (P < 0·05) on survival of transplanted teeth: periodontal disease as the reason for recipient site tooth extraction, fewer than 25 present teeth and Eichner index Groups B1 to C. Cox regression analysis examined five factors: age, smoking habit, recipient site extraction caused by periodontal disease, fewer than 25 present teeth and Eichner index. This analysis showed that two of these factors were significant: fewer than 25 present teeth was 2·63 (95% CI, 1·03-6·69) and recipient site extraction caused by periodontal disease was 3·80 (95% CI, 1·61-9·01). The results of this study suggest that long-term survival of transplanted teeth in males is influenced not only by oral bacterium but also by occlusal status., (© 2012 Blackwell Publishing Ltd.)

The aim of this study was to investigate the usage of tooth autotransplantation in dental clinics which offer the treatment and evaluate its practicality. Participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. A total of 614 teeth from 552 patients (37 dentists) ranging in age from 17 to 79 (mean age: 44·1) were examined. Cumulative survival rate and mean survival time were calculated using the Kaplan-Meier method, and log rank test was used for analysis of factors. The mean number of autotransplantation patients per clinic per year was 1·4. Upper third molars constituted 36·8% of donor teeth, while 37·1% were lower third molars. The lower first molar region was the most common recipient site at 32·6%, followed by the lower second molar region (28·0%). Prosthodontic treatment of transplanted teeth involved coverage with a single crown (72·5%) and abutment of bridge (18·9%). A total of 102 transplanted teeth were lost owing to complications such as attachment loss (54·9%) and root resorption (25·7%). The cumulative survival rate in cases where donor teeth had complete root formation was 90·1% at 5 years, 70·5% at 10 years and 55·6% at 15 years. The mean survival time was 165·6 months. Older age was a significant risk factor (P < 0·05) for survival. In cases where suitable donor teeth are available, autotransplantation of teeth may be a plausible treatment option for dealing with missing teeth in dental clinics., (© 2011 Blackwell Publishing Ltd.)

Background: We evaluated the clinical significance and prognostic value of histopathological features of bladder cancer, such as subepithelial growth patterns and tumor growth pattern at the invasion front., Methods: In total, 130 patients newly diagnosed with non-muscle invasive bladder cancer and underwent transurethral resection between 1998 and 2009 were enrolled. Subepithelial growth patterns consisting of endophytic growth pattern (EGP) and von Brunn's nest involvement (VBNI) were investigated using hematoxylin and eosin-stained slides, and their frequency of occurrence, prognostic value, and correlation with other clinicopathological features was evaluated., Results: EGP and VBNI were found in 40 (30.8%) and 5 (3.9%) of the 130 cases, respectively. Of the 26 pT1 tumors, the growth pattern at the invasion front was trabecular in 17 (65.4%) and infiltrative in 9 (34.6%). Although 8 (47.1%) of 17 trabecular tumors coexisted with EGP, no cases with infiltrative tumors had EGP (p = 0.023). VBNI correlated with high tumor grades (p = 0.006) and lymphovascular involvement (p = 0.026). The multivariate Cox proportional hazards analysis revealed that tumor diameter less than 3 cm (p = 0.04) and intravesical bacillus Calmette-Guérin therapy (p = 0.004) were independent favorable prognostic factors for recurrence-free survival, whereas tumor stage was an independent poor prognostic factor for disease progression (p = 0.006)., Conclusions: Subepithelial growth patterns were not a significant prognostic factor in this study. Additionally, no tumors with an infiltrative growth pattern coexisted with EGP, suggesting that determining the presence of EGP might be helpful for managing non-muscle invasive bladder cancers.

Background: Conjunctival oedema is commonly observed in patients with allergic conjunctivitis and can be induced by histamine. In animal models of allergic conjunctivitis, conjunctival oedema is generally evaluated by measuring the extravasation of Evans blue dye into the conjunctiva. A limitation of this method is that it only allows evaluation at a single time point. The aim of the present study was to investigate kinetic changes in histamine-induced bulbar oedema., Methods: Evans blue dye was injected intravenously into male guinea pigs. Histamine eye-drops were administered 30 min later. One group of animals received levocabastine (an antihistamine) eye-drops 10 min before histamine challenge. A digital camera was used to obtain images of the bulbar conjunctiva at 1 min intervals until 30 min after histamine challenge. The conjunctivas were then harvested, and the concentration of Evans blue was measured. The ImageJ software was used to analyse the images by counting the number of absolute pixel values., Results: The degree of conjunctival oedema increased progressively until 20 min after histamine challenge and then stabilised. Correspondingly, the number of absolute pixel values increased significantly until 5 min after histamine challenge, then increased gradually until the 20 min time point and finally plateaued. Pixel values were significantly lower in animals treated with levocabastine than in control animals. A significant correlation was observed between the pixel values of the conjunctival images and the concentration of Evans blue in the conjunctiva., Conclusions: This is the first study to have quantitatively evaluated kinetic changes in histamine-induced bulbar oedema by means of image analysis.

A 39-year-old man presented with left scrotal pain which lasted for 3 days. The laboratory test showed slightly elevated C-reactive protein and lactate dehydrogenase whereas α-fetoprotein and β-human chorionic gonadotropin were normal. Scrotal Doppler ultrasound test demonstrated an oval-shaped hypoechoic lesion and enhanced magnetic resonance imaging revealed an avascular lesion in the left testis with the rim enhancement. He underwent left high orchiectomy. The histopathological examination revealed segmental testicular infarction with partial necrosis.

Neuroendocrine (NE) cells are widely distributed in the acini and ducts of the normal prostate gland and produce neurosecretory products, which affect growth, differentiation and regulation of secretory function. Prostatic NE carcinoma is a rare situation and the NE differentiation in prostate adenocarcinoma appears to be characterized by poor prognosis, rapid tumor progression and the androgen-independent state, for which there is currently no successful therapy. We report a case of NE differentiated prostatic carcinoma, which was diagnosed as adenocarcinoma initially and the tumor progressed rapidly with NE differentiation during androgen suppression therapy.

We report a case of a metastatic intrapelvic tumor arising from esophageal cancer. The patient, a 74-year-old man, visited our hospital with the chief complaint of gross hematuria. Magnetic resonance imaging and cystoscopy revealed a huge intrapelvic tumor which invaded the bladder, rectum, sigmoid colon and left ilium. The patient underwent total pelvic evisceration with ileal conduit and colostomy. Pathologic diagnosis of the intrapelvic tumor was moderately differentiated squamous cell carcinoma. Preoperatively, gastrointestinal fiberscopy revealed an esophageal tumor, and biopsy showed moderately differentiated squamous cell carcinoma. Finally, the intrapelvic tumor was diagnosed as metastatic tumor from esophageal cancer.

Genital tuberculosis occurring in the spermatic cord is a rare disease. A 70-year-old man presented with a mass on the left side of the scrotum which had been painless and had gradually enlarged over the previous 4 months. Surgical excision was performed. The tumorous mass was located in the spermatic cord but did not connect with the testis or epididymis. The removed specimen was 15 x 20 x 15 mm in size and weighed 6 g. Histopathological diagnosis was tuberculosis. At present, 27 months after surgery, recurrence has not been found.

Rupture of a renal artery aneurysm is an acute surgical event associated with high mortality. We report a case of retroperitoneal hemorrhage from a spontaneously ruptured renal artery aneurysm. A 73-year-old woman complained of left flank and abdominal pain. She consulted our department and left retroperitoneal hemorrhage was recognized by abdominal computerized tomography. Selective left renal arteriography revealed a saccular aneurysm arising from the ventral branch of the renal artery, and did not show extravasation of contrast material from the aneurysm. Since it was difficult to remove the aneurysm with preservation of the involved renal unit, we performed left nephrectomy.

Avulsion of ureter without renal injury is rarely caused by blunt trauma, only 28 cases having been reported in Japan. A 33-year-old male was admitted to our hospital 1 month after blunt abdominal trauma at work. He complained of left flank pain and macroscopic hematuria. Under the suspicion of renal or ureteral injury, drip infusion urography and abdominal computerized tomography revealed an extravasation from the left upper ureter and urinoma formation in the retroperitoneal cavity. In order to reduce the inflammation, the urinoma was drained. The retrograde pyelogram revealed complete obstruction at the left upper ureter, 20 cm from the left ureteral orifice. Urinary tract reconstruction, end-to-end ureteral anastomosis, was performed under the diagnosis of left ureteral avulsion. Drip infusion urography revealed normal ureteral healing without stricture formation at 2 years after reconstruction.

Objective and Design: We investigated the anti-inflammatory effects of 16 beta-methyl-17 alpha,21-diesterified glucocorticoids which are well known as potent topical glucocorticoids in man on endotoxin-induced uveitis (EIU) in rats., Material: Female Lewis rats were used., Treatment: Glucocorticoids were instilled (0.01%-1.0%) or subcutaneously injected (0.1-10 mg/kg) to rats., Methods: To elicit EIU, LPS (500 micrograms/kg) was injected into the footpad of rats. Twelve hours after LPS injection, cell number in aqueous humor was counted by flow cytometry. Endotoxin-induced in vivo tumor necrosis factor-alpha (TNF-alpha) production was also examined., Results: 16 beta-methyl-17 alpha,21-diesterified glucocorticoids showed no effects or some enhancement of cell infiltration into the aqueous humor in EIU by topical instillation. Systemic injection of these glucocorticoids showed only weak inhibition of cell infiltration and TNF-alpha production. On the other hand, betamethasone phosphate strongly inhibited the cell infiltration and TNF-alpha production. Combined systemic injection of 16 beta-methyl-17 alpha,21-diesterified glucocorticoids and betamethasone phosphate reduced the inhibitory effects of the latter., Conclusions: These results suggest that 16 beta-methyl-17 alpha,21-diesterified glucocorticoids might act as partial agonists of glucocorticoid in rats.

The anti-inflammatory effects of betamethasone and its derivatives (betamethasone 21-phosphate, betamethasone 21-acetate, betamethasone 17-valerate, clobetasol 17-propionate and betamethasone dipropionate) on endotoxin-induced uveitis (EIU) in rats was investigated. Among the compounds examined, betamethasone, betamethasone 21-phosphate, betamethasone 21-acetate and clobetasol 17-propionate strongly inhibited cell infiltration into the aqueous humor in the EIU by instillation into the eye in a dose-dependent manner (0.01-1.0%) and by systemic administration (1 mg kg-1). On the other hand, betamethasone 17-valerate and betamethasone dipropionate showed only weak inhibitory effects or enhancement of cell infiltration by instillation into the eye (0.01-1.0%) and by systemic administration (1 mg kg-1). Combined systemic administration of betamethasone dipropionate and betamethasone reduced the inhibitory effect of betamethasone on cell infiltration and gene expression of IL-1 beta. In an in vitro interleukin-8 (IL-8) release assay, betamethasone showed stronger inhibition of the IL-8 release from rat peritoneal exudate cells (PEC) than betamethasone dipropionate, and simultaneous addition of betamethasone dipropionate with betamethasone reduced the inhibitory effect of the latter. These results suggest that the betamethasone derivative betamethasone dipropionate might behave as an anti-glucocorticoid in rats.

The authors conducted a morphological investigation of age-related changes in the lens of male Fischer rats at 6, 12, 18 and 24 months of age. At 6 months, there were no abnormalities of particular note other than slight swelling of the subcapsular fibers. Moreover, other than a slight decrease in the density of epithelial cells and slightly more extensive fiber swelling, there were no remarkable changes seen in the lens at 12 months. At 18 months of age, posterior invasion by the processes of the cortical lens fibers toward the lens capsule and slight swelling of the anterior cortical fibers were seen in addition to the above-mentioned changes. By 24 months of age, these changes had become more noticeable, with further reduction in the density of epithelial cells, swelling and degeneration of both anterior and posterior fibers and extension of the thin processes of the equatorial fibers toward the capsule. However, the bow configuration at the equator appeared almost normal. These findings indicate that the age-related changes in the Fischer rat lens occurred in the epithelial cells and superficial layer of the cortical fibers, subsequently leading to the loss of clarity in the lens.

In developing chick embryos, hydrocortisone induces cataract formation following a decrease in lens glutathione content but an increase in lipid peroxide content in lens, blood and liver. The preventive effects of ascorbic acid 2-O-alpha-glucoside (AA-2G) on these parameters were compared on cataract formation with those of ascorbic acid (AsA) and ascorbic acid 2-O-phosphate (AA-2P). In these tissues, AA-2G inhibited a decrease in glutathione content and an increase in lipid peroxide content more effectively than either AsA or AA-2P. Various tissues including lens and liver have alpha-glucosidase activity, strongly suggesting that AsA is enzymatically liberated from AA-2G in these tissues. In summary, these results suggest that AA-2G exerts a potent anti-cataract activity via a reduction in oxidative damage through AsA release.

We determined the concentration dependent effects of arachidonic acid between 0.3 and 30 x 10(-6) M on corneal epithelial migration, in an organ culture system of the rabbit cornea. With 3 x 10(-6) M arachidonic acid, corneal epithelial migration was maximally stimulated by 51%. The cyclooxygenase inhibitors, indomethacin, ketoprofen, flurbiprofen and diclofenac sodium also all had a tendency to stimulate corneal epithelial migration at low concentrations (0.1 or 1 x 10(-6) M). However, the inhibitory effect of epithelial migration was observed at higher concentration (100 x 10(-6) M) of these compounds. On the other hand, the selective 5-lipoxygenase inhibitor, AA-861 over a concentration range from 0.1 to 10 x 10(-6) M maximally inhibited corneal epithelial migration by 25%. These results suggest that during wound healing some of the increased release of arachidonic acid may be derived from a metabolite of the 5-lipoxygenase pathway which may in turn hasten wound closure.

The effects of linolenic acid hydroperoxide (LAPO) on isolated rat lenses were investigated, because they are believed to be cataractogenic in vivo. They were also compared with the effect of linolenic acid (LA), source of LAPO. Rat lenses, which were exposed for 5 hr to either 210 microM or 420 microM LAPO, became cloudy and this change was associated with increases in the level of malondialdehyde (MDA), a breakdown product of lipid peroxide, and decreases in non-protein thiol (NP-SH) content. Concomitantly, there were changes in cation contents: Na+ and Ca2+ were increased whereas K+ and Mg2+ were decreased. The changes in the levels of the above parameters, correlated with the concentration and the treatment time of LAPO to which the lenses were exposed. The increase of MDA was 2-4-fold over normal level and was consistent with those in cataractous lenses of the human and experimental animal models. On the other hand, if the lenses were exposed to LA, the only change observed was a small alteration of cationic content. If the lenses were cultured for an additional 24 hr in the absence of either LA or LAPO, the cation content continued to change only in those lenses which were previously exposed to LAPO. These results show that at concentrations of lipid peroxides, which are associated with the development of cataract in the human and animal models, there are changes in vitro in cation content, MDA and NP-SH levels, which accompany the development of a lens opacity.

The effect of ascorbic acid 2-O-alpha-glucoside (AA-2G) on hydrocortisone (HC)-induced lens opacity in developing chick embryo was examined and compared with those of ascorbic acid (AsA) and ascorbic acid 2-phosphate (AA-2P). The opacity was dose-dependently inhibited by a single administration of 10 or 20 mumol/egg of AA-2G and by three repeated administrations of 1, 3 or 10 mumol/egg of AA-2G. AA-2G was the most effective among the three compounds. Glucose did not enhance the preventive effect of AsA against HC-induced opacity, and neither dehydro ascorbic acid nor glucose also prevented HC-induced cataract. In the histological study, we observed many small vacuoles in the nuclear region of the opaque lens treated with HC. AA-2G inhibited the formation of such vacuoles, an effect closely correlated with the prevention of cataract formation.

l-Tetrahydroberberine-d-camphor sulfonate (THB-CS) possessed an inhibitory effect on apomorphine-induced chewing movement in a similar manner to that of tetrahydroberberine (THB). Both compounds enhanced barbiturate-induced hypnosis. They did not have an anticonvulsant effect on convulsive seizures induced by bicuculline, pentetrazole or strychnine. THB and THB-CS blocked dopamine-stimulated adenylate cyclase activity. These compounds showed almost equipotent affinities to dopamine D1 (3H-SCH-23390) and D2 (3H-spiperone) receptors but did not have significant affinity to mu-opioid, muscarinic and alpha 2-adrenergic receptors, and benzodiazepine binding sites. Furthermore, both compounds did not elicit cataleptogenic behavior, even at very high doses. These data suggest that THB and THB-CS have a central depressant effect through both D1 and D2 dopaminergic receptors and may have different modes of action from that of standard neuroleptics.