Mechanisms of pinacidil-induced vasodilatation

The mechanism of the vasodilator effect of pinacidil was examined. Pinacidil (0.1–100 μM) inhibited the increases in cytosolic Ca²⁺ ([Ca²⁺]_i) and muscle tension due to norepinephrine in rat aorta. In contrast, a Ca²⁺ channel blocker, verapamil, inhibited the norepinephrine-stimulated [Ca²⁺]_i more strongly than the contraction. Higher concentrations of pinacidil (3–100 μM) inhibited the verapamil-insensitive portion of the contraction and [Ca²⁺]_i. An inhibitor of ATP-sensitive K⁺ channels, glibenclamide, antagonized the inhibitory effect of low concentrations ( 10 pM) of pinacidol. Pinacidil did not change the contraction induced by Ca²⁺ in vascular smooth muscle permeabilized with Staphylococcus aureus -toxin. Norepinephrine (in the presence of GTP), 12-deoxyphorbol 13-isobutyrate (in the absence of GTP), and treatment with GTP_γS potentiated the contraction of permeabilized smooth muscle induced by the addition of Ca²⁺. Pinacidil (100 μM) inhibited the potentiation due to GTP_γS or noepinephrine but not to phorbol ester. These results suggest that pinacidil has dual effects on vascular smooth muscle contraction. At lower concentrations (>0.1 μM), it decreases [Ca²⁺]_i, possibly by activating ATP-sensitive K+ channels. At higher concentrations (> 3 μM), it may additionally inhibit the receptor-mediated, GTP-binding protein-coupled phosphatidyl inositol turnover.     

The relation between the plasma lipoprotein pattern and the waist/hip ratio in non-diabetic individuals

Relations between lipoprotein indices and the waist/hip ratio (WHR) were examined in normoglycemic subjects (124 women and 63 men). Among women, an atherogenic lipoprotein pattern was strongly associated with WHR. The relation was greater than that of the lipoprotein pattern with either the body mass index or the subscapular/triceps ratio, and was independent of these adiposity measures. The association between low-density-lipoprotein cholesterol (LDL-cholesterol) and WHR was much stronger in thinner women than in those more obese (r = 0.64 vs r = 0.22, p = 0.001 for difference). Men had a more atherogenic lipoprotein pattern than women; however, with allowances for WHR the lipoprotein patterns were similar. These findings suggest that: (1) WHR is more strongly related to plasma lipoproteins than other adiposity measures; (2) there is effect modification by the extent of adiposity for the relation between LDL-cholesterol and WHR; and (3) the adipose distribution may be important in explaining lipoprotein differences between men and women.     

A combined treatment with 8 MHz radiofrequency hyperthermia, HPC-adriamycin, immunotherapy, radiation, systemic chemotherapy and irradiation for invasive bladder carcinoma

Hyperthermia was induced for the treatment of invasive bladder carcinoma in order to study its usefulness. The subjects were 12 cases of invasive bladder cancer; including 5 cases of T2, 3 cases of T3, 2 cases of T4, and 2 cases of recurrence after total cystectomy. As previous treatment, 4 patients received radiotherapy and the other received TUR, systemic chemotherapy, and intravesical injection of anticancer drugs. For hyperthermia treatment, a Thermotron RF-8 was used for heating a deep seated tumor. Each case received hyperthermia 2 to 10 times. Combined therapy included injection of HPC-adriamycin into the urinary bladder in 5 cases, immunotherapy in 3 cases, M-VAC therapy in one case, radiotherapy in one case, radiotherapy and intra-arterial injection in one case, and Peplomycin and OK-432 local injection in one case. The treatment results showed a 75% effectiveness; with CR in 4 cases, PR in 5 cases, MR in 2 cases and PD in one case. Three patients died and 9 survived. Of four patients who had received radiotherapy as a previous treatment 3 cases obtained CR and one case MR. Therefore, it was considered that a favorable treatment effect with hyperthermia could be obtained after radiotherapy.     

Effects of subacute toluene exposure on neuronal and glial marker proteins in rat brain

The behavior of marker proteins of neurons (gamma-enolase) and glial cells (alpha-enolase, beta-S100 protein and creatine kinase-B) was investigated quantitatively by using enzyme immunoassay systems in toluene-exposed rat brains. Three groups of animals were exposed to toluene vapor at 300 ppm, 1000 ppm, and 3000 ppm, respectively, 8 h/day, 6 days/week, for 2 weeks. After subacute repeated solvent exposure, both neuron-specific gamma-enolase and glial marker proteins displayed an overall concentration-dependent increase tendency in separate brain regions. In cerebrum, only the 3000 ppm group showed a significant increase in alpha-enolase by 27% and creatine kinase-B (CK-B) by 26%. alpha-Enolase and gamma-enolase exhibited a pronounced elevation in cerebellum relative to other brain regions, while beta-S100 protein appeared to be the most markedly altered marker in brainstem. The development of gliosis, which is a frequent phenomenon following CNS damage, is presumed to be responsible for the elevation of glial marker content. Energy metabolism disruption in brain tissues may also bring about the compensatory oversynthesis of glycolytic enzymes such as gamma-enolase, alpha-enolase and CK-B. The dose-dependent alteration patterns following toluene exposure suggest the feasibility of using these brain specific markers to evaluate solvent-induced CNS effects.     

Leukotriene B4 production in children with steroid-responsive nephrotic syndrome

Leukotriene B₄ (LTB₄) production in polymorphonuclear leucocytes (PMN) was examined in ten children with steroid-responsive nephrotic syndrome (SRNS) before, during, and after steroid administration. Comparison of LTB₄ production was made in 14 children with non-inflammatory disease who were not receiving steroid therapy. No significant change was noted in PMN LTB₄ biosynthesis in children with SRNS throughout any phase of the disease. Furthermore, there was no significant difference in LTB₄ biosynthesis in PMN between SRNS patients before steroid therapy and patients with non-inflammatory disease. These findings suggest that inhibition of LTB₄ production is not involved in the mechanism underlying steroid action in SRNS.     

A case of acute focal bacterial nephritis

Acute focal bacterial nephritis refers to a renal mass caused by acute focal infection. We report a case of acute focal bacterial nephritis, herein. The case was in a 56-year-old woman, who was hospitalized with the chief complaint of left flank pain, chills and fever. Intravenous pyelography suggested the presence of a mass in the upper pole of the left kidney. Ultrasonography showed a hypoechoic mass, CT scan revealed a round, low density mass. Antibiotic therapy resulted in resolution of symptoms, and a follow-up CT scan and ultrasonography showed complete resolution of the renal mass.     

Effects of various drugs on bladder function in conscious restrained-denervated rats placed in a restraining cage and produced by transection of the hypogastric nerve

We evaluated the effects of various intravenously administered drugs, which had been shown to influence bladder function in anesthetized and/or conscious rats, on the cystometrogram in conscious restrained-denervated rats (produced by transection of the hypogastric nerve) placed in a restraining cage in comparison to those in conscious restrained-intact rats (with the hypogastric nerve intact) placed in a restraining cage. The bladder capacity in the restrained-denervated rats was smaller than that in restrained-intact rats and did not change when they were transferred to a wide cage, but the bladder capacity of the restrained-intact rats decreased following transfer to the wide cage. Therefore, the activity of the hypogastric nerve in conscious rats appears to be stimulated by restraint. Atropine suppressed the amplitude of the micturition contraction (time to micturition in the cystometrogram). In the restrained-denervated rats, thiopental and indomethacin increased the bladder capacity at almost the same doses as those in restrained-intact rats, but it took a higher dose of morphine to increase the bladder capacity than in restrained-intact rats. These findings suggest that cystometrography in restrained-denervated rats is a useful method for evaluating the effect of a newly developed agent on bladder function without any influence from the hypogastric nerve.     

Antimicrobial activity of AO-128, a novel inhibitor of alpha-D-glucosidase, against anaerobic bacteria]

The in vitro antimicrobial activity of AO-128, an inhibitor of alpha-D-glucosidase, was evaluated against anaerobic bacteria of 45 reference strains (12 genera, 44 species). AO-128 inhibited no strains tested at a concentration of 1,600 micrograms/ml. The results strongly suggested that this compound would not have any influence on the human intestinal microflora, a majority of which is composed of anaerobic bacteria.     

Operative findings in camptodactyly of the little finger.

In five of six cases of camptodactyly in which an abnormality of the flexor tendon was examined at operation, the flexor digitorum superficialis tendon was hypoplastic and there was no continuity of the normal tendon between the muscle belly and bony insertion. The proximal end of the flexor digitorum superficialis tendon was attached to the palmar aponeurosis and the flexor tendon sheath of the ring finger in two patients, to the palmar aponeurosis in one, to the undersurface of the transverse carpal ligament in one and to the flexor tendon sheath of the ring finger in one. The tenodesis effect of the abnormal tendon of the flexor digitorum superficialis is considered to play an important role in the cause and rapid increase of the deformity of camptodactyly.