Interaction between the septal area and the subfornical organ in the control of water intake induced by thirst-eliciting procedures

Rats bearing lesions in the septal area followed by lesions in the subfornical organ were submitted to various thirst-eliciting procedures. The rats with hyperdipsia induced by lesions of the septal area drank more water than either during the control period or after lesion of the subfornical organ under the same thirst-eliciting or angiotensin-liberating stimuli (polyethyleneglycol, isoproterenol, water deprivation and ligation of the inferior vena cava). The overdrinking elicited by lesions in the septal area was blocked after lesion of the subfornical organ. Neither hypovolemia, nor hypotension or water deprivation could elicit increased water intake in animals whose subfornical organ had been destroyed. Animals with lesions in the subfornical organ showed decreased water intake after cellular dehydration. The results obtained suggest that the subfornical organ acts as a more important structure than the septal area in the regulation of water intake elicited by angiotensin, with two opposite effects: a direct one facilitating water intake, and an indirect one inhibiting the septal area. The septal area has an inhibitory effect on the subfornical organ and on water intake.     

Polygoacetophenoside, A New Acetophenone Glucoside from Polygonum multiflorum1

Polygoacetophenoside ( 3), a new acetophenone glucoside, was isolated from POLYGONUM MULTIFLORUM (Polygonaceae), together with quercetin 3- O-galactoside ( 1) and arabinoside ( 2). The structure of the new glucoside was deduced to be 2,3,4,6-tetrahy-droxyacetophenone 3- O-beta- D-glucoside ( 3) by its chemical and spectral data.     

Kinetics of hepatic transport of 4-methylumbelliferone in rats. Analysis by multiple indicator dilution method

Hepatic elimination of 4-methylumbelliferone (4MU), which has been used as a model compound for conjugative metabolism, was studied by means of a multiple indicator dilution (MID) method in the isolated perfused rat liver. Using this method, three intrinsic hepatic clearances, CL _int,inf , CL _{int,eff, and} CL _{int,seq, which represent the influx, efflux, and sequestration processes, respectively, were obtained. When the dose was increased from a low dose (50 g/rat liver) to a high dose (3000 g/rat liver), the hepatic availability of 4MU increased from 0.11 to 0.73. With increasing dose, the} CL _{int,eff value increased approximately two times, while the} CL _{int,seq value decreased to approximately one-third. The remarkable dose dependence of hepatic availability was due to nonlinearity in both} CL _{int,eff and} CL _{int,seq values. However, the} CL_int,inf value was almost independent of dose. The dose-dependent change in CL_int,seq might be explained by the saturation of conjugative metabolism of 4-MU, while the increase in the CL _{int,eff value with increasing dose might be partly explained by the nonlinear tissue binding of 4-MU, since the tissue unbound fraction determined by an ultrafiltration method using liver homogenate increased approximately 1.5 times at higher concentration of 4-MU compared to that at lower concentrations. In addition, based on a comparison of the individual intrinsic clearances, i.e.}, CL _int,inf , CL _{int,eff, and} CL _{int,seq, the major determining process of the apparent hepatic intrinsic clearance of 4MU is thought to be the sequestration process at the high dose. However, at the low dose, the membrane transport process (influx and efflux processes) as well as the sequestration process also determine the apparent hepatic intrinsic clearance}.     

Can random bladder biopsies be eliminated after bacillus Calmette–Guérin therapy against carcinoma in situ?

Purpose

Intravesical bacillus Calmette–Guérin (BCG) is the standard of care for bladder carcinoma in situ (CIS). The response to BCG therapy against CIS is generally assessed by random bladder biopsy (RBB). In this study, we examined the necessity of routine RBB after BCG therapy.

Methods

We retrospectively identified 102 patients who were initially diagnosed with CIS with or without papillary tumor and received subsequent 6–8-week BCG therapy. Thereafter, all patients underwent voiding cytology analysis, cystoscopy, and RBB to evaluate the effects of BCG therapy. We evaluated the association between clinical parameters (voiding cytology and cystoscopy findings) and the final pathological results by RBB specimens.

Results

According to the pathological results of RBB, 30 (29%) patients had BCG-unresponsive disease (remaining urothelial carcinoma was confirmed pathologically) and 20 were diagnosed with CIS. Positive/suspicious voiding cytology and positive cystoscopy findings were well observed in patients who had BCG-unresponsive disease compared with their counterparts (p?=?0.116, and p?<?0.001, respectively). The sensitivity (Sen.), specificity (Spe.), positive predictive value (PPV), and negative predictive value (NPV) of voiding cytology were 50%, 68%, 39%, and 77%, respectively. The values for cystoscopy findings were as follows: Sen.: 87%, Spe.: 57%, PPV: 46%, and NPV: 91%. The values for their combination (having either of them) were as follows: Sen.: 100%, Spe.: 44%, PPV: 43%, and NPV: 100%.

Conclusion

RBB after BCG therapy for patients with negative voiding cytology and negative cystoscopy may be omitted because their risk of BCG-unresponsive disease is significantly low (NPV: 100%).

     

Aspects chirurgicaux de la segmentation des veines hépatiques basés sur la veinographie hépatique

Conclusion Nous pensons que nous devons clairement préciser non seulement la distribution des branches de la v. porte, mais aussi celle des v. hépatiques drainant une tumeur afin de faciliter au mieux la résection hépatique à réaliser tout en conservant un maximum de parenchyme fonctionnel. Lorsqu'un segment doit être réséqué, il est nécessaire d'étudier la morphologie des veines et de leurs branches par phlébographie hépatique préopératoire afin de bien préciser les limites de la résection en fonction du siège de la tumeur.     

Strain differences in age-associated change in testosterone 6β-hydroxylation in Wistar and Dark Agouti rats

This study examines strain differences in testosterone (T)-hydroxylations between Wistar and Dark Agouti (DA) rats of both genders. The DA rat, an animal model, is a poor metabolizer of such drugs as debrisoquine, which are metabolized by cytochrome P450 (CYP) 2D. T-16α-, 2α-hydroxylations, which are linked to CYP2C11, were catalyzed at similar rates by the microsomes of both strains. In contrast, the liver microsomes from mature male DA rats catalyzed T-6β-hydroxylation, the CYP3A mediated activity, at higher rates (～ 2-fold) than Wistar rat liver microsomes did. There was no difference between immature male DA and Wistar rats for T-6β-hydroxylation, indicating that the activity in male DA rat increases with maturation. Polyclonal antibodies raised against rat liver microsomal CYP3A2 and a CYP3A inhibitor, troleandomycin (TAO), effectively inhibited T-6β-hydroxylation by liver microsomes from both strains of rats. The level of T-6β- hydroxylation activity correlated well with the amount of CYP3A protein in the microsomes in mature as well as in immature male and female Wistar and DA rats. Northern blot analysis repeatedly indicated that the cellular contents of CYP3A2 mRNA are slightly (～ 20%) higher in the liver of mature DA rats than in that of mature Wistar rats. These results indicate that the increased levels of CYP3A are responsible for the increased T-6β-hydroxylation activity and protein in DA rat.     

Functional MRI of the human brain responses to olfactory stimulation

Image artifacts such as signal loss or distortion due to intravoxel phase dispersion at the skull base are problematic in analysis by functional MRI (fMRI). Since the olfactory center of the brain is located in the medial temporal and basal frontal areas, it is a challenge to try to detect the Blood Oxygenation Level Dependent (BOLD) effect during fMRI at olfactory stimulation. We examined 20 normal volunteers with a 1.5-T MR system, employing multishot, interleaved echo-planar imaging (EPI). Olfactory stimulation was performed with 2-methyl-1, 3-cyclo-pentanedione, a caramel-like fragrance, by presenting it for 20 seconds with two cycles of rest-stimulus paradigm. Sites of functional activation were identified by correlation analysis with a threshold of p < 0.01. Most commonly activated areas were the orbitofrontal and primary olfactory cortices. Mild activation was also observed in the cingulate gyrus, lateral temporal cortex, cerebellum, parietal and occipital lobes. These results indicate that olfactory stimulation participates in the emotion and behavior processes. Interestingly, broad activation in the "silent" area of the frontal and temporal lobe was also observed in some cases. Multishot EPI was a useful method to evaluate brain activation at the basal level on fMRI.     

Serosurvey of wild rodents for Rickettsioses (spotted fever, murine typhus and Q fever) in Java Island, Indonesia

The prevalence of antibodies against spotted fever group rickettsia (SFGR), murine typhus and Q fever were investigated in wild rats captured in Indonesia. Sera of 327 rats were collected from Jakarta and Boyolali on Java Island. The prevalences of antibodies against SFGR and murine typhus were 128 (39.1%) and 48 (14.7%), respectively. Antibodies against Q fever were not detected in these serum samples. Antibodies against SFGR were found in all species of rats (20.8–51.9%). The antibody positive rate against murine typhus in Rattus norvegicus (38.0%) was significantly higher than that in other rat species (0–4.8%, p < 0.01). The antibody positive rates against SFGR and murine typhus in rats captured in Jakarta were significantly higher than those in rats captured in Boyolali (p < 0.01). In this survey, all species of rats had antibodies against SFGR, indicating that the 4 species of tested rats (R. norvegicus, R. rattus, R. exulans, R. tiomanicus) were infected with SFGR and that SFGR may infest the whole of Java Island. Most of the rats that were antibody-positive against murine typhus were captured in Jakarta. Therefore, R. norvegicus and R. rattus are likely to be important hosts of murine typhus in Jakarta. The antibody-positive rates against SFGR and murine typhus in rats captured in the dry season were significantly higher than those in rats captured in the rainy season. This may coincide with the active periods of ticks and fleas in Indonesia.     

Antiarrhythmic effect and its underlying ionic mechanism of 17beta-estradiol in cardiac myocytes.

1. The effects of oestrogens on action potential and membrane currents were examined in single guinea-pig atrial myocytes. 2. 17Beta-estradiol (3-10 microM) shortened the action potential duration without significant changes in the resting membrane potential. E-4031 (1 microM) markedly prolonged the action potential duration and induced early afterdepolarization, and 17beta-estradiol (10 microM) abolished it. 3. When cells were perfused in isoproterenol-containing solution, action potentials due to abnormal automaticity caused by membrane depolarization developed, and were also inhibited by 17beta-estradiol. 4. Under voltage clamp conditions, the voltage-dependent Ca2+ currents consisted of both T-(I(Ca,T)) and L-type (I(Ca,L)). 17Beta-estradiol reduced I(Ca,L) concentration-dependently, while it (10 microM) suppressed I(Ca,T) only by approximately 10%. 17Beta-estradiol did not affect time courses of I(Ca,L) inactivation, but it shifted the steady-state inactivation curve to more negative potentials. 5. 17Beta-estradiol (10 microM) did not affect the time-dependent K+ current (I(K)), referred to as I(Kr) and I(Ks) and inwardly rectifying K+ current. However, 17beta-estradiol (30 microM) or diethylstilbestrol (10 microM) inhibited K+ currents. 6. DES and ethinylestradiol (EES) also suppressed I(Ca,L), but testosterone and progesterone failed to inhibit I(Ca,L) The potency of the inhibitory effect on I(Ca,L) was DES> EES> 17beta-estradiol. 7. 17Beta-estradiol and DES also inhibited the cyclic AMP-enhanced I(Ca,L), but cyclic GMP in the pipette or pretreatment of L-NAME could not block the effects of oestrogen on I(Ca,L). 8 These results suggest that oestrogen specifically has antiarrhythmic effects, possibly by acting the L-type Ca2+ channels. The antiarrhythmic effects of oestrogens may contribute to the cardioprotective actions of oestrogens.     

Development and assessment of the pharmaceutical management and guidance services for inpatients considering clinical value and economy]

We developed pharmaceutical management and guidance services for inpatients in a ward of circulatory medicine, considering clinical and economical standpoints. In these services, pharmacists deliver drugs prescribed for inpatients with individual drug information papers, explain to them about their drugs using information papers and give counsel. Since most of the patients were aged people, developing many kinds of diseases and taking many kinds of drugs, they had many problems such as lack of knowledge of the effects of drugs. First, we surveyed views of patients, physicians and nurses on these services. Consequently, all of them advised us that "pharmacists should explain to patients about the prescribed drugs using information papers." The patients preferred pharmacists as expositors of drugs to physicians or nurses. The physicians considered that "pharmacists have to attach importance to clinical information and package-inserts of drugs and explain to patients about drug information using pamphlet in response to the understanding of patients." The nurses wanted to cooperate with pharmacists in "improving medication compliance." On the basis of these views, we improved our services. Next, we made a survey of patients' knowledge about their drugs. We found that in the patients the level of knowledge concerning "ways," "effects" and "reasons" of taking drugs and that of "compliance" and "satisfaction in taking drugs" were improved through these services. The patients reentered in the hospital kept a high level. The ratio of patients taking drugs by themselves increased. Last, we also applied this method to wards of "blood and collagen diseases" and "pediatrics." The demand for these services increased smoothly. We compared these services based on our method with all other services by hospital pharmacists from the viewpoint of economy. We found that only our service method was beneficial.