Topical KINOSTAT™ ameliorates the clinical development and progression of cataracts in dogs with diabetes mellitus

Objective To determine whether topical administration of the aldose reductase inhibitor Kinostat™ can ameliorate the onset or progression of cataracts in dogs with naturally occurring diabetes mellitus (DM). Materials and Methods A randomized, prospective, double‐masked placebo control pilot study was conducted with 40 dogs newly diagnosed with DM with no or minimal lens changes. Twenty‐eight dogs received Kinostat™ and 12 dogs received placebo. Procedures Owners administered the agent into both eyes three times daily for 1 year and compliance was monitored with log sheets. Complete ophthalmic examinations were performed on dilated eyes at the time of enrollment and 1, 2, 3, 6, and 12 months into treatment. Cataract severity was assessed on a scale of 0–3. At 12 months, full bloodwork, including HbA1C and blood Kinostat^TM levels were performed. Results After 12 months of treatment, the cataract score in the placebo group significantly increased with seven dogs (14 eyes) developing mature cataracts, two dogs (4 eyes) developing cortical opacities, and one dog (2 eyes) developing equatorial vacuoles with mild punctate cortical opacities. In contrast, the cataract score in the Kinostat^TM treated dogs was significantly less with seven developing anterior equatorial vacuoles, two developing incipient anterior cortical cataracts, and four developing mature cataracts. In fact, the cataract scores of the Kinostat^TM group at 12 months did not significantly increase from the score at the time of enrollment. The HbA1C values between the two groups after 12 months of treatment were similar, and no blood levels of Kinostat^TM were found in any enrolled dog. Conclusion The onset and/or progression of cataracts in dogs with DM can be significantly delayed by topical administration of Kinostat™.     

链脲佐菌素和四氧嘧啶联合注射建立犬I型糖尿病模型

旨在探索链脲佐菌素和四氧嘧啶联合注射建立犬I型糖尿病模型的最佳剂量。本试验选取18只9~12月龄、平均体重为（5.09±0.30）kg的健康中华田园犬,随机分为6组（每组3个重复,每个重复1只）。按链脲佐菌素和四氧嘧啶不同剂量混合分组,其中Ⅰ组（20 mg·kg^-1/40 mg·kg^-1）、Ⅱ组（30 mg·kg^-1/50 mg· kg^-1）和Ⅲ组（40 mg·kg^-1/60 mg·kg^-1）进行单次静脉注射;Ⅳ组（10 mg·kg^-1/20 mg·kg^-1）、Ⅴ组（15 mg·kg^-1/25 mg·kg^-1）和Ⅵ组（20 mg·kg^-1/30 mg·kg^-1）进行两次静脉注射,两次注射间隔为24 h。通过注射后血糖、葡萄糖耐量、血液生理生化和胰腺组织形态学变化来评价各组建模效果。结果显示：1）Ⅰ组和Ⅳ组的空腹血糖始终处于正常水平,Ⅱ组和Ⅲ组连续7 d超过15 mmol·L^-1,Ⅴ组和Ⅵ组虽有上升,但试验期间均未超过10 mmol·L^-1;2）葡萄糖耐量试验显示,各组血糖均在15 min升高至峰值,之后Ⅰ组和Ⅳ组逐渐下降到注射前水平,Ⅴ组血糖虽下降但未达到注射前水平,Ⅱ组、Ⅲ组和Ⅵ组持续保持高血糖水平;3）各组血常规指标均在正常生理范围内,Ⅲ组的丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）、尿素（UREA）和肌酐（CREA）均超过正常生理范围;4）胰腺组织形态学显示,Ⅱ组和Ⅲ组的胰岛结构被明显破坏。综上所述,对犬使用30 mg·kg^-1+50 mg·kg^-1的链脲佐菌素和四氧嘧啶联合单次静脉注射,血糖值连续7 d大于15 mmol·L^-1且未造成严重的肝肾毒性,可有效建立I型糖尿病模型。     

Clinical Value of Fructosamine Measurements in Non-healthy Dogs

Ninety-three unhealthy dogs (including some with diabetes mellitus or insulinoma) of different ages, sex and breeds were divided into 10 groups according to their pathology. Serum fructosamine concentrations were determined using a commercial colorimetric nitroblue tetrazolium method. Diabetic dogs had the highest fructosamine concentrations (454.85±149.34 mol/L). Dogs with insulinoma had significantly lower fructosamine concentrations (202.80±31.22 mol/L), similar to those with leishmaniosis (202.83±99.83 mol/L). Fructosamine concentrations in non-healthy dogs, except those with diabetes mellitus, insulinoma or leishmaniosis, were within the reference limits previously reported.     

Serum Fructosamine: A Reference Interval for a Heterogeneous Canine Population

Eighty-nine healthy dogs (44 males, 45 females) of different breeds, 1-12 years of age, living under varied feeding and environmental conditions, were sampled to evaluate a reference interval for serum fructosamine using a nitroblue tetrazolium photocolorimetric method. The analytical assay was evaluated by calculation of within-run and between-day variations. The results were approximately normally distributed and the calculated reference interval was 192.6-357.4 µmol/L (mean 275.0 µmol/L, standard deviation 41.2 µmol/L). No significant differences attributable to sex or age were observed. This reference interval is wider than those previously reported in less heterogeneous groups of dogs and in those from other geographical zones. The fructosamine values in serum from 3 diabetic dogs all exceeded the upper limit of the reference interval.     

山茱萸不同提取物降血糖作用研究

以正常小鼠和四氧嘧啶糖尿病小鼠为动物模型,分别对山茱萸乙醚提取物、乙酸乙酯提取物和乙醇提取物的降血糖作用进行研究。结果表明,山茱萸3种提取物组与模型组比较,均可显著降低四氧嘧啶糖尿病小鼠血糖水平(P0.01)。山茱萸3种提取物组间比较,乙酸乙酯提取物组的降血糖作用最明显(P0.05)。正常小鼠对照实验表明,山茱萸3种提取物对正常小鼠的血糖无明显影响(P0.05)。本试验筛选出山茱萸乙酸乙酯提取物为山茱萸的降血糖活性成分。     

蜂巢中总黄酮测试方法的探讨

用乙醇作溶剂浸渍蜂巢,浸渍时间分别为1～15d。用751G分光光度计,在波长510nm处,测定其滤液中的总黄酮含量,分析蜂巢浸渍液中总黄酮的变化规律。试验表明蜂巢浸渍7天测定其滤液总黄酮含量为最佳。     

Assessment of Alloxan-Induced Diabetic Rats as a Periodontal Disease Model Using a Selective Cyclooxygenase (COX)-2 Inhibitor

Several recent studies have reported that alloxan-treated rats with long-term hyperglycemia can develop naturally occurring periodontal disease (PD). Our previous studies detected dental caries in the same model. Therefore, these two lesions of different etiologies are expected to occur concurrently. In this study, we evaluated the use of diabetic rats as a PD model by employing a selective COX-2 inhibitor reported to be effective against PD. Six-week-old female F344 rats were divided into 3 groups: intact rats (control), alloxan-induced diabetic rats fed a standard diet (AL) and alloxan-induced diabetic rats fed a diet containing 0.01% etodolac (AL+Et). The animals were euthanized at 26 weeks of age, and their oral tissues were examined histopathologically. Gingivitis, marginal periodontitis and alveolar bone resorption were markedly enhanced along with dental caries in the AL group compared with the control group. However, the COX-2 inhibitor had no effect on periodontal inflammation in the AL+Et group. In addition, in the AL group, periodontitis was notably nonexistent around the normal molars, and gingivitis was scarcely worse than that in the control group. In the diabetic rats, the progression of periodontal inflammation was closely correlated with the severity of adjacent dental caries, and marginal periodontitis was frequently continuous with apical periodontitis. In conclusion, an alloxan-induced diabetic rat is not a model of PD but of dental caries. It is probable that in this model, hyperglycemia may enable crown caries to progress to apical periodontitis, while the associated inflammation may rostrally expand to surrounding periodontal tissue.     

实验性猕猴1型糖尿病模型的建立及评价

7～10岁健康猕猴15只,随机分为Ⅰ、Ⅱ、Ⅲ组,每组5只,分别按照100、125、150mg/kg的剂量一次性静脉注射链脲菌素,连续观察血糖、血浆C肽和胰岛素浓度的动态变化,观察期15周.结果:与注射链脲菌素前比较,注射后1周,Ⅰ组猕猴血糖浓度明显升高,血浆C肽和胰岛素浓度显著下降(P＜0.01),随后趋于正常水平,而Ⅱ、Ⅲ组猕猴血糖浓度明显升高并在随后的时间内持续维持在高水平,血浆C肽和胰岛素浓度持续维持在低水平(P＜0.001),Ⅲ组动物至15周全部死亡.结论:按照125mg/kg的剂量一次性给猕猴静脉注射链脲菌素,可成功复制1型糖尿病动物模型,其维持高血糖和低胰岛素及C肽浓度至少15周.     

Transient hyperglycaemia in a prediabetic dog treated with prednisone and cyclosporin A

A dog with immune-mediated haemolytic anaemia developed transient hyperglycaemia and glucosuria requiring insulin therapy in association with prednisone and cyclosporin A therapy. Following short-term therapy with insulin and cyclosporin A, the dog remained on prednisone therapy but required no further insulin therapy for 12 weeks, at which time the dog became permanently diabetic. We hypothesise that prednisone and cyclosporin A contributed to insulin resistance in a prediabetic dog with suboptimal endogenous insulin concentration and that the degree of insulin resistance decreased when cyclosporin A therapy was discontinued.