Chronic acid ingestion promotes renal stone formation in rats treated with vitamin D3

OBJECTIVE: Although hypercalciuria, a well-established adverse effect of vitamin D3, can be a risk factor of renal stone formation, the risk of nephrolithiasis has not been well defined. The consumption of a diet high in acid precursors is often cited as a risk factor for the development of calcium-based kidney stones. In the present study, we investigated the effect of chronic acid ingestion on kidney stone formation in rats treated with calcitriol (1-25[OH]2 D3). METHODS: Control rats (C-C), calcitriol-treated rats (C-V; three treatments of 0.5 microg of calcitriol per week) and acid-ingested (water containing 0.21 mol/L NH4Cl), calcitriol-treated (three treatments of 0.5 microg of calcitriol per week) rats (A-V) were fed in metabolic cages. After 1 month, urine, blood, kidney and bone samples were analyzed. RESULTS: The A-V rats exhibited elevated serum calcium concentrations, urinary calcium and phosphate excretion, urinary type I collagen cross-linked N-peptide (NTx)/creatinine values, mRNA expression of osteopontin in the kidney, and renal calcium contents as well as decreased bone mineral densities, compared with the C-C and C-V rats. Urinary citrate excretion was lower and NaDC-1 mRNA expression in the kidney was higher in the A-V rats than in the C-C and C-V rats. Calcium phosphate kidney stones were found in the A-V rats. CONCLUSIONS: The ingestion of NH4Cl, an acid precursor, promotes calcium phosphate kidney stone formation in calcitriol-treated rats. The chronic intake of a diet rich in acid precursors may be a risk factor for the development of kidney stones in subjects who are being treated with calcitriol.     

Comparison of factors related to hospitalization versus home care of elderly

This study was done to identify factors affecting present hospitalization versus home care in 4,578 elderly subjects representing 87.1% of the elderly population living in S. city near Osaka. Subjects or their families were asked by interviews regarding the age of the subjects, the kind of persons living together in the family unit, the kind of housing, the number of rooms in the family dwelling, and health conditions. Subjects were also asked whether he or she could walk unassisted and whether home care would be preferred in case of an illness. Among the 153 hospitalized subjects, ability to walk, age, and the number of rooms were all significant factors, in decreasing order. Among the 1,193 persons who preferred home care in case of an illness, the number of rooms, age, ability to walk, and the size of the family unit were all significant factors, in decreasing order. Among subjects who could not walk unassisted, the number of rooms was the main factor determining their admission and not preferring home care if their condition worsened. Thus, although the ability to walk is the major factor among the factors we investigated, housing conditions are also important if home care is to be possible.     

Coagulopathy in disseminated intravascular coagulation due to abdominal sepsis: determination of prothrombin fragment 1 + 2 and other markers.

To estimate the degree of coagulopathy in abdominal sepsis, we measured the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PIC) by the enzyme-linked immunosorbent assay in 38 patients with disseminated intravascular coagulation (DIC). In 20 patients with DIC due to abdominal sepsis, plasma levels of F1 + 2, TAT and PIC were 2.6 nmol/l, 27.9 micrograms/l and 1.5 micrograms/ml, respectively, with a mean antithrombin III (AT III) activity of 41.7%. F1 + 2, TAT, PIC and AT III levels were 4.7 nmol/l, 75.8 micrograms/l, 8.8 micrograms/ml and 70.9% in 18 patients with DIC as the result of malignancy. Though AT III levels in DIC due to sepsis were lower than those in DIC due to malignancy, the levels of F1 + 2, TAT and PIC in the former were not significantly more increased than those in the latter. The plasma levels of F1 + 2 were positively correlated with TAT and PIC in DIC patients with malignancy; however, there was no correlation between F1 + 2 and TAT or PIC in DIC patients with sepsis. In addition, the levels of serum albumin in the two groups were similar. These results suggest that activation of coagulation and fibrinolytic systems may not be so prominent in cases of DIC due to abdominal sepsis, compared to related events in DIC due to malignancy. It is also suggested that the depletion of AT III in cases of sepsis is not only caused by a consumption related to intravascular coagulation or to an alternate distribution of protein.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early and midterm results of the arterial switch operation for transposition of the great arteries in Japan

A total of 267 infants and children who underwent the arterial switch operation for transposition of the great arteries in the 6 years before Jan. 1, 1988 in six main Japanese institutions were entered into this review. The current status of patients surviving more than 1 year after the operation were evaluated along with early operative results. One hundred forty-six patients had an intact ventricular septum, 103 had a significant ventricular septal defect, and 18 had so-called Taussig-Bing anomaly of the transposition type. Eighteen patients were less than 28 days of age, 73 were 1 to 5 months of age, and 176 were older than 6 months of age at the time of operation. The overall mortality rate was 35% in the first 3 years and 12% in the more recent 3 years. There was a significant difference between the overall mortality rate of primary and two-stage repair (22% versus 10%, p = 0.047) in patients with intact ventricular septum. The overall mortality rate in patients with type B or C coronary arteries of Yacoub, and Radley-Smith's classification was significantly higher than that of other types of arteries (86% versus 18%, p = 0.0001). A total of 156 patients survived more than 1 year after the operation, and 44 children (28%) were noted to have supravalvular pulmonary stenosis (greater than 20 mm Hg). This complication was more common in patients operated on in the newborn period. Trivial or mild aortic regurgitation was noted in 29 patients (19%) and was more common in patients with two-stage than with primary repair (24% versus 14%). Aortic regurgitation was significantly more prevalent in patients in whom coronary arteries were implanted into slits or U-shaped defects than in those whose arteries were implanted into punched-out holes made on the pulmonary root (28% versus 8%, p = 0.049). Normal sinus rhythm was present in 97% of 154 patients and left ventricular ejection fraction was within the normal range in 97% of 115 patients at catheterization 1 to 5 months after the operation.     

Action of Isoflurane on the Substantia Gelatinosa Neurons of the Adult Rat Spinal Cord

Background: Although isoflurane, a volatile anesthetic, can block the motor response to noxious stimulation (immobility and analgesia) and suppress autonomic responsiveness, how it exerts these effects at the neuronal level in the spinal cord is not fully understood.

Methods: The effects of a clinically relevant concentration (1 rat minimum alveolar concentration [MAC]) of isoflurane on electrically evoked and spontaneous excitatory/inhibitory transmission and on the response to exogenous administration of the [gamma]-aminobutyric acid type A receptor agonist muscimol were examined in lamina II neurons of adult rat spinal cord slices using the whole cell patch clamp technique. The effect of isoflurane on the action potential-generating membrane property was also examined.

Results: Bath-applied isoflurane (1.5%, 1 rat MAC) diminished dorsal root-evoked polysynaptic but not monosynaptic excitatory postsynaptic currents. Glutamatergic miniature excitatory postsynaptic currents were also unaffected by isoflurane. In contrast, isoflurane prolonged the decay phase of evoked and miniature [gamma]-aminobutyric acid type A receptor-mediated inhibitory postsynaptic currents and increased the amplitude of the muscimol-induced current. Isoflurane had little effect on action potential discharge activity.     

Differential induction of cytochrome P-450 by the enantiomers of trans-stilbene oxide

Optically pure (+)- and (-)-trans-stilbene oxide (TSO) enantiomers were administered to immature male Sprague-Dawley rats. (+)-TSO was the more potent inducer of liver microsomal cytochrome P-450-dependent monooxygenases. The greater potency of (+)-TSO may be explained on the basis of stereoselective metabolism since a far greater concentration of TSO was found in liver microsomes of (+)-TSO-treated rats. Furthermore, of the enzymes known to metabolize TSO, cytosolic epoxide hydrolase turned over the (-)-TSO enantiomer at a faster rate, consistent with the greater persistence of the (+)-enantiomer. Although this report is of chiral effects in potency of enzyme induction, stereoselective metabolism (i.e. disposition) rather than inherent structural characteristics (recognition) may be responsible for these effects.     

The role of intracellular Ca2+ in the degranulation of skinned mast cells

The intracellular pH of rat peritoneal mast cells was slightly acidic and compound 48/80 induced a decrease in the cytoplasmic pH of these cells. By means of chemical skinning, it was revealed that perfusion with Ca2+ or inositol 1,4,5-trisphosphate (IP3) induced degranulation dose-dependently in mast cells at concentrations higher than 10 microM and 0.1 microM, respectively. Na+ was essential for the release of histamine from mast cells. An assay based on the binding of 45Ca to mast cell fragments revealed that the intracellular Ca store of the mast cell is located in the endoplasmic reticulum. IP3 liberated Ca from the endoplasmic reticulum.     

A case of acute hepatitis E associated with multidrug hypersensitivity and cytomegalovirus reactivation

A 65-year-old Japanese man was hospitalized because of acute hepatitis and severe cholestasis due to hepatitis E virus (HEV) infection combined with a drug reaction to a cold preparation. He died of disseminated intravascular coagulation and severe intestinal bleeding due to systemic cytomegalovirus reactivation following the development of severe eruptions with marked eosinophilia due to drug hypersensitivity to taurine and ursodeoxycholate preparations. The close interaction between viral infection or reactivation and drug hypersensitivity was considered as a pathophysiology in this case, which emphasizes the need for further study of the immunological mechanism of the interaction.     

The alloantigen-specific immunosuppressive activity of estradiol-chlorambucil conjugate (KM2210) and its beneficial effect on allogeneic bone marrow transplantation in mice.

KM2210, a conjugate of estradiol and chlorambucil (CBL), which was originally developed as an anti-breast cancer agent, inhibits proliferative response of human mononuclear cells to alloantigens in mixed lymphocyte culture in a dose-dependent manner, but has no effect on their response to phytohemagglutinin. Neither estradiol benzoate nor CBL alone showed these unique actions. The suppressive effect of KM2210 on MLC was abrogated by adding of anti-transforming growth factor-beta (TGF-beta) antibody to the culture, but was not affected by the addition of interleukin-2, suggesting that KM2210, unlike CBL, displays its actions via TGF-beta. In experimental allogeneic bone marrow transplantation using mice, daily oral administration of KM2210 (2 mg/kg/day) for 30 days posttransplant significantly inhibited the alloantigen-specific immune reactions. Furthermore, the survival rate of the KM2210-treated mice was significantly higher than that of the cyclosporine-treated (2 mg/kg/day, p.o.) mice, and no adverse effect of KM2210 on hematopoietic recovery was found. These results strongly suggest possible clinical benefits of KM2210 as a new immunosuppressive agent for the prevention and treatment of graft-versus-host disease and other allospecific immune reactions.