Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.     

Peroxisome proliferator-activated receptor delta (PPARdelta), a novel target site for drug discovery in metabolic syndrome.

The development of new treatments for metabolic syndrome is urgent project for decreasing the prevalence of coronary heart disease and diabetes mellitus in the advanced countries. Peroxisome proliferator-activated receptor (PPAR)alpha and gamma agonists have shed light on the treatment of hypertriglyceridemia and type 2 diabetes mellitus, respectively. Among PPARs, analysis of the PPARdelta functions is lagging behind because specific PPARdelta agonists have not been developed. The appearance of new PPARdelta agonists is brightening the prospects for elucidating the physiological role of PPARdelta. PPARdelta is a new target for the treatment of metabolic syndrome. In particular, the fact that fatty acid oxidation and energy dissipation in skeletal muscle and adipose tissue by PPARdelta agonists lead to improved lipid profile, reduced adiposity and insulin sensitivity is a breakthrough. It seems that treatment of PPARdelta agonists operate similarly to the caloric restriction and prolonged exercise. We suggest that the physiological role of PPARdelta may be an indicator for switching from glucose metabolism to fatty acid metabolism. To receive new benefits of PPARdelta agonists against metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue, we need to unveil more details on the functions of PPARdelta itself and its agonists in the future.     

Study of the effects of dopamine hydrochloride on alpha 1-adrenoceptors in rat kidney

We studied the number and affinity of catecholamine receptors in SD rat kidney by radioreceptor technique. The following conclusions were obtained: 1) By using 3H-prazosin, the numbers of alpha 1-receptor (Bmax) in rat renal cortex were greater than those in rat kidney medulla. As for affinity (Kd), the significance was not recognized between the two. Bmax of the rat renal cortex to 3H-prazosin binding was 96.1 fmol/mg protein, and Kd was 0.17 nM, and for the rat renal medullar these values were 44.5 fmol/mg protein and 0.13 nM, respectively. 2) By measurement of D1-receptor using 3H-SKF38393 in the rat renal cortex in the Scatchard plot analysis, positive cooperativity was observed under the low concentration of hot ligand which was less than 1 nM. But at the concentration of hot ligand over 1 nM, the plots showed a straight line. Bmax of the rat renal cortex to 3H-SKF38393 was 2.5 pmol/mg protein and Kd was 5.3 nM. 3) Based on displacement by dopamine for 3H-prazosin binding to rat renal cortex, it was surmised that high concentration of dopamine had an affinity to alpha 1-adrenoceptors. 4) There was no change in the Kd and Bmax of alpha 1-receptor in the rat renal cortex after incubation of samples with low concentration of dopamine. However, in the case of high concentration of dopamine, a remarkable decrease of the affinity (Kd) of alpha 1-adrenoceptor was observed.     

l-DOPA induces concentration-dependent facilitation and inhibition of presynaptic acetylcholine release in the guinea-pig submucous plexus

Neurotransmitter- or neuromodulator-like actions ofl-DOPA were investigated with intracellular recordings from submucous plexus neurons of the guinea-pig caecum.l-DOPA at 30 nM augmented the amplitude of fast EPSPs, but did not affect depolarizations elicited by puff application of acetylcholine (ACh). The augmenting effect ofl-DOPA on the fast EPSPs was counteracted byl-DOPA methyl ester. The fast EPSPs were depressed by 10 μMl-DOPA, but transiently augmented after rinsing the drug.l-DOPA methyl ester did not affect the inhibitory action ofl-DOPA on the fast EPSPs, but antagonized the potentiation following the inhibition. The depolarization elicited by exogenously applied. ACh was inhibited by 10 μMl-DOPA. Intracellular Ca²⁺ concentrations ([Ca²⁺]_i) of the neuronal soma were measured with fura-2 microfluorophotometry. The transient increase in the [Ca²⁺]_i evoked by the somatic action potential (Δ[Ca²⁺]_AP) was facilitated by 30 nMl-DOPA, but decreased by the drug at 10 μM. It is concluded thatl-DOPA at low concentrations enhances the Δ[Ca²⁺]_AP, increasing the neurotransmitter release, but at high dose diminishes the Δ[Ca²⁺]_AP, inhibiting the neurotransmission.     

Biodistributions of 201Tl in tumor bearing animals and inflammatory lesion induced animals

The accumulation of 201Tl in tumor and inflammatory tissues were small. However, this nuclide showed a high concentration in viable tumor tissue, less in connective tissue (containing inflammatory tissue), and was not seen in necrotic tumor tissue regardless of the time after administration of 201Tl(I)-chloride. In inflammatory lesions, 201Tl accumulated in subcutaneous tissue infiltrated with neutrophils and macrophages, and quite large amounts of this nuclide were accumulated in subcutaneous tissue and sites where neutrophils were crowded. Most 201Tl existed in a free form in the fluid of tumor and inflammatory tissues regardless of the time after administration. A small amount of this nuclide was localized in the nuclear, mitochondrial and microsomal fractions in these tissues, and the nuclide was bound to protein in these fractions. The distribution of 201Tl(III)-chloride in tumor bearing animals was essentially the same as that of 201Tl(I)-chloride.     

Evidence for a defect in urinary concentrating ability in primary aldosteronism and its reversal by adrenal surgery

Of 15 patients with primary aldosteronism, 7 had idiopathic adrenal hyperplasia (IHA) and 8 had aldosterone-producing adenoma (APA). In order to determine any renal problems involved in the treatment, the renal clearance of these patients was analyzed and the results compared with those obtained from 12 patients with essential hypertension. With water diuresis or under antidiuresis status, levels of urine volume, Cosm and CH2O in patients with APA were greater (p less than 0.05-p less than 0.001) than those of patients with essential hypertension, while the fractional tubular sodium delivery of the former patients was lower than that of the latter patients (p less than 0.001 or less than 0.05). A similar tendency was observed in clearance studies in patients with IHA, although to a lesser extent. Adrenal surgery for patients with APA normalized these values, but administration of trilostane (3 beta-hydrosteroid dehydrogenase inhibitor) to patients with IHA failed to improve these values. These results indicate that impaired urinary concentrating ability as well as reduced urinary diluting capability is a common feature of primary aldosteronism. Such impaired renal function was improved only in patients with APA after adrenal surgery.     

Surgical treatment for coronary artery aneurysm

Two successful cases of the surgical treatment for coronary artery aneurysm (non-Kawasaki disease) were reported. The first case had a saccular aneurysm on the left circumflex coronary artery (LCx) #14. Resection of the LCx aneurysm was performed subsequent to single vessel coronary artery bypass grafting (CABG) to the distal portion of LCx#14 under the cardioplegic cardiac arrest. The second case had aneurysms on both the left anterior descending artery (LAD) #7 (fusiform) and the LCx#11 (saccular). After double vessel CABG to LAD#7 and LCx#11, ligation or resection of two aneurysms was performed successfully. Postoperative courses have been uneventful with good angiographic results achieved. Since these surgical procedures demonstrated safety, the patients are expected to achieve a good long-term prognosis.     

Portsite and intraabdominal metastases of unsuspected gallbladder carcinoma after laparoscopic cholecystectomy: Report of a case

We herein report a rare case of portsite metastasis of gallbladder carcinoma which occurred after laparoscopic cholecystectomy. A 64-year-old man underwent laparoscopic cholecystectomy at another hospital for symptomatic cholecystolithiasis. The histological examination revealed an adenocarcinoma of the gallbladder infiltrating the entire wall. Despite the physician's advice the patient refused any additional treatment. Thirteen months after surgery he visited our hospital because of a palpable mass at the scar of the right trocar incision. The nodule was removed and histological examination confirmed metastasis from the gallbladder carcinoma.