Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes.

AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) has various extra-pancreatic actions, in addition to its enhancement of insulin secretion from pancreatic beta cells. The GLP-1 receptor is produced in kidney tissue. However, the direct effect of GLP-1 on diabetic nephropathy remains unclear. Here we demonstrate that a GLP-1 receptor agonist, exendin-4, exerts renoprotective effects through its anti-inflammatory action via the GLP-1 receptor without lowering blood glucose. METHODS: We administered exendin-4 at 10 µg/kg body weight daily for 8 weeks to a streptozotocin-induced rat model of type 1 diabetes and evaluated their urinary albumin excretion, metabolic data, histology and morphometry. We also examined the direct effects of exendin-4 on glomerular endothelial cells and macrophages in vitro. RESULTS: Exendin-4 ameliorated albuminuria, glomerular hyperfiltration, glomerular hypertrophy and mesangial matrix expansion in the diabetic rats without changing blood pressure or body weight. Exendin-4 also prevented macrophage infiltration, and decreased protein levels of intercellular adhesion molecule-1 (ICAM-1) and type IV collagen, as well as decreasing oxidative stress and nuclear factor-κB activation in kidney tissue. In addition, we found that the GLP-1 receptor was produced on monocytes/macrophages and glomerular endothelial cells. We demonstrated that in vitro exendin-4 acted directly on the GLP-1 receptor, and attenuated release of pro-inflammatory cytokines from macrophages and ICAM-1 production on glomerular endothelial cells. CONCLUSIONS/INTERPRETATION: These results indicate that GLP-1 receptor agonists may prevent disease progression in the early stage of diabetic nephropathy through direct effects on the GLP-1 receptor in kidney tissue.

Erythromycin ameliorates renal injury via anti-inflammatory effects in experimental diabetic rats.

AIMS/HYPOTHESIS: Recent studies have shown that the inflammatory process is involved in the pathogenesis of diabetic nephropathy. Fourteen-membered ring macrolides, including erythromycin, have anti-inflammatory, as well as antibacterial effects. The aim of this study was to investigate the renoprotective effects of erythromycin in streptozotocin (STZ)-induced diabetic rats. METHODS: STZ-induced diabetic rats were treated orally with erythromycin (5 mg/kg body weight) or vehicle every day for 8 weeks. To evaluate the effect of erythromycin treatment, we measured urinary albumin excretion, and examined the following in the kidney: histological changes, the expression of intercellular adhesion molecule-1 (ICAM-1), macrophage infiltration, and nuclear factor-kappa B (NF-kappaB) activity. RESULTS: Erythromycin significantly reduced urinary albumin excretion without affecting blood glucose levels and blood pressure. Erythromycin also attenuated glomerular hypertrophy, mesangial expansion, macrophage infiltration and ICAM-1 expression in renal tissues. The expression of the gene encoding TGFB1 (also known as TGF-beta1), type IV collagen protein production and NF-kappaB activity in renal tissues were increased in diabetic rats and reduced by erythromycin treatment. CONCLUSIONS/INTERPRETATION: Erythromycin prevented renal injuries without changes of blood glucose levels and blood pressure in experimental diabetic rats. These results suggest that the renoprotective effects of erythromycin are based on its anti-inflammatory effect via suppression of NF-kappaB activation. Modulation of microinflammation with erythromycin may provide a new approach for diabetic nephropathy.

[Clinical results of thermoradiotherapy for recurrent lung cancers--comparison of results with radiotherapy alone].

From October 1986 through December 1989, 18 patients with locally recurrent lung cancer were treated by local hyperthermia combined with radiotherapy at the Kawasaki Medical School Hospital. Nine patients were initially treated by radiotherapy for inoperable lung cancer or as adjunct postoperative therapy. The other 9 were initially treated by chemotherapy or operation. Local heat was applied with a 13.56 MHz radiofrequency (RF) capacitive heating equipment, twice a week after radiotherapy, for 45-60 minutes per session. The results were compared with 17 patients with locally recurrent tumors which were treated by radiation therapy alone between January 1981 and September 1986. Tumor temperatures of two patients were measured directly by thermocouples inserted into the tumors which partially attached to the chest wall. As we were unable to measure tumor temperatures in the other 16 because of the anatomical difficulty, we measured the temperatures of the esophagus as near as possible to these lesions. Based on thermometry results, it was estimated that the maximum tumor temperatures were about 40-41 degrees C. The local response rates (CR + PR) were 25% in patients treated with combined therapy and 7% in those with RT alone. The median survivals after onset of retreatment were 10.7 months and 5.0 months, a statistically significant difference being demonstrated. Severe complications were not seen in this treatment.

[Radiotherapy of prostatic cancer].

From 1976 to 1988, 33 patients with a prostatic cancer were treated with radiotherapy at Kawasaki Medical School. The age of these patients ranged from 45 to 82 with the average being 69 years. The actuarial 5 year survival rates for patients in stages B (n = 6), C (n = 12), D1 (n = 5), or D2 (n = 10) were 100%, 65%, 50%, and 40%, respectively. The for those with an adenocarcinoma that was well differentiated (n = 5), moderately differentiated (n = 13), or poorly differentiated (n = 15) was (were?) 100%, 58%, and 41%, respectively.

Effect of ethanol induced occlusion of the renal artery in rabbit kidney implanted with VX2 carcinoma.

The effects of injection of absolute ethanol into the renal artery were investigated in 13 rabbit kidneys previously implanted with VX2 carcinoma. Eight rabbits with implanted tumors served as controls. The effects were evaluated by angiography and histology. Three days after implantation, tumors were demonstrated by angiography as relatively hypovascular areas in the subcapsular cortex of the kidneys. Following angiography, absolute ethanol (0.3 ml/kg) was injected into the renal artery. Repeat angiography with barium sulphate was performed after an additional 3 days (10 ethanol treated animals, 2 controls), 10 days (2 treated, 1 control) or 14 days (1 treated, 0 control). In treated animals the tumors were markedly smaller in comparison with those of the control group. The occlusion procedure, however, did not completely eradicate tumor cells. The histologic study of the implanted tumor confirmed the findings previously reported that viable tumor cells still remained in the peripheral portions of infarcted areas. This study demonstrated the beneficial, though not curative, short-term effects of transcatheter renal artery treatment with absolute ethanol in malignant renal tumors.

[The effect of a static magnetic field on hamsters bearing melanoma--cell cycle analysis by flow cytometry].

Hamsters bearing Greene's melanoma in the side were exposed to an almost uniform 0.2 Tesla (T) magnetic field for three hours. Tumors were extirpated immediately after and 3, 12 and 21 hours after the exposure, then were minced and meshed into a single cell suspension. Cells were stained with anti BrdU FITC and Propidium Iodide for cell cycle analysis with FACStar. The distribution of each cycle phase of the exposed group was somewhat unequal to that of the control group. Namely, there was a decrement of G1% at three and twelve hours after exposure and an increment of S% (p = 0.01) at twelve hours after exposure.

[Clinical experiences with intraluminal irradiation using 198Au grains in the treatment of bile duct carcinoma].

Three cases of a bile duct carcinoma were treatment with radiotherapy, using intracatheterized 198Au grains. The intracatheter 198Au grains, placed in an inner tube, were inserted into a percutaneous transhepatic catheter. The number of 198Au grains used depended upon the length of the tumor. Tips of plastic were placed between the grains to improve the spatial and temporal dose allocation. The number of grains used can be changed quite easily, according to the length of the tumor, and the period of insertion in our cases was shorter than for a 192Ir wire. These three patients also received external irradiation and, since completion of treatment, two have continued to do well for the past 5 months. There have been no systemic or local complication.

[A case of triple cancer--gastric, esophageal and hepatocellular carcinoma].

A case of triple cancer involving a tubular adenocarcinoma of the stomach, a squamous cell carcinoma of the esophagus, and hepatocellular carcinoma of the live is reported. These three cancers had been diagnosed while the patient was alive and later were confirmed by autopsy. The esophageal cancer and hepatocellular carcinoma were found almost simultaneously, 6 years after surgery for the gastric cancer. Although many cases of triple cancer have been reported, a triple cancer of this combination is very rare (0.3% of all cases of triple cancer), our case being the fifth such case in Japan.

Computed tomography of basal ganglia calcifications in pseudo- and idiopathic hypoparathyroidism.

It is well known that patients with pseudo (PHP)- and idiopathic (IHP) hypoparathyroidism are frequently associated with intracranial calcifications. The relative sensitivity of computed tomography (CT) and conventional skull radiography in detecting basal ganglia calcifications was studied in two patients with PHP and six with IHP. CT was more sensitive: the detection rate was 71% (5/7) for CT and 14% (1/7) for skull radiography. Furthermore, patients with more prolonged hypocalcemia showed a higher incidence of calcifications. Thus, CT was useful as a diagnostic technique in the early detection of calcified basal ganglia.

[Effectiveness of radiation therapy in metastatic bone tumors].

The effectiveness of radiation therapy for metastatic bone tumor in 61 patients with 80 lesions has been evaluated. Relief from pain resulted in 87% all the treated lesions and this continued for more than two years in eight lesions of seven patients. There was no statistical difference in the pain relief achieved among the sites and the histologies of the primary tumors, and also no difference was noted as to the treated regions. Pain relief from the lesions of a squamous cell carcinoma tended to begin with smaller doses when compared with that of an adenocarcinoma. Our results suggest that radiation therapy in general appears to be an effective technique in achieving long term control of pain, but for some patients those with a generalized metastases or an uncontrolled primary tumor, for example, this tedious treatment has limited value and so should be withheld.

Usefulness of liver scan using 99mTc-phytate in diagnosis of partial diaphragmatic eventration.

Partial diaphragmatic eventration, when occurring at uncommon sites, is difficult to diagnose when only using a plain X-p and fluoroscopy. We experienced an unusual variety of this disorder. In order to diagnose this case, liver scintigraphy using 99mTc-phytate was performed, and we were able to make a definite diagnosis without other invasive examinations.

99mTc-colloid kits from the view point of the accretion in the bone marrow--with special reference to comparison with 198Au-colloid.

With 9 kinds of available 99mTc-colloid kits for RES imaging, especially from the aspect of RES imaging of the bone marrow, observations were conducted on pH, the presence of free 99mTcO4(-), labelling efficiency, rabbit blood clearance, the uptake in RES, urinary excretion, as well as the scintigraphy with rabbits and clinical cases. Compared to 198Au-colloid, marrow to liver ratio was found to be about the same, but its uptake to the spleen and liver was greater. In particular its urinary excretion was much more marked than 198Au-colloid, and in clinical use the bladder was more often delineated. This fact seems to suggest that it is desirable to develope a 99mTc-colloid more suitabale for the bone marrow scintigraphy.

An evaluation of hepatobiliary scintigraphy with 99mTc-pyridoxylideneisoleucine.

From our experience with 30 cases, we conclude that 99mTc-PI is useful for assessment of hepatobiliary diseases and is much preferable to the 131I-labeled compounds.