Effect of phytic acid on postprandial serum uric acid level in healthy volunteers: a randomized, double-blind, crossover study.

Phytic acid, a constituent of various plants, has been related to health benefits. Phytic acid has been shown to inhibit purine nucleotide metabolism in vitro and suppress elevation of plasma uric acid levels after purine administration in animal models. This study investigated the effect of phytic acid on postprandial serum uric acid (SUA) in humans. This randomized, double-blind, crossover design study included 48 healthy subjects with normal fasting SUA. Subjects consumed a control drink and a phytic acid drink with purine-rich food, and serum and urine uric acid levels were measured for 360 min after purine loading. Phytic acid lowered the incremental area under the curve (0-360 min) and incremental maximum concentration of SUA after purine loading (p < 0.05); tended to lower cumulative urinary uric acid excretion (0-360 min) after purine loading (p < 0.10); and suppressed postprandial SUA in this clinical study. Altogether, our findings suggest that phytic acid may play a beneficial role in controlling postprandial SUA.

Lactobacillus pentosus strain b240 suppresses pneumonia induced by Streptococcus pneumoniae in mice.

AIMS: Oral administration of probiotics has been known to improve inflammatory responses against infectious diseases. Here, we describe the inhibitory effect of oral intake of heat-killed Lactobacillus pentosus strain b240 (b240) on pneumococcal pneumonia in a murine experimental model. METHOD AND RESULTS: The mice treated with oral b240 for 21 days before Streptococcus pneumoniae infection exhibited prolonged survival time and less body weight loss, compared with saline-treated control mice. Mild pneumonia with significantly reduced secretion of inflammatory cytokines/chemokines according to related mitogen-activated protein kinase signalling molecules (phosphorylated c-Jun N-terminal kinase) was found in b240-treated mice, whereas severe pneumonia with hypercytokinemia was evident in control mice. Prominent reduction in the number of pneumococci and elevated expression of Toll-like receptor 2 and 4 in the lung tissues was concomitantly noted in b240-treated mice. CONCLUSIONS: These findings indicate that b240 has inhibitory effects on pneumococcal pneumonia induced by Strep. pneumoniae infection and improves inflammatory tissue responses, resulting in reduced damages to the respiratory tissues. SIGNIFICANCE AND IMPACT OF THE STUDY: These results demonstrate that oral administration of b240 might protect host animals from Strep. pneumoniae infection by augmentation of innate immune response.

Effect of cilostazol, a phosphodiesterase III inhibitor, on experimental thrombosis in the porcine carotid artery.

Thrombus formation in the carotid artery is one of the common causes of transient ischemic attacks and stroke. Platelet aggregation seems to be an essential component in these processes. The present study was conducted to determine the ability of cilostazol, a phosphodiesterase III inhibitor, to prevent formation of totally occlusive thrombus in a porcine carotid artery, in comparison with ticlopidine. Castrated male Yorkshire pigs were allocated to control (n=8), cilostazol (30 mg/kg, twice a day [b.i.d] for 2 days, n=8), and ticlopidine (50 mg/kg, b.i.d. for 3 days, n=7) groups. The endothelium of the right common carotid artery was injured with electrical stimulation (150 microA) without constriction and blood flow in this region was monitored by Doppler flow probe. Arterial blood was sampled during electrical stimulation for the measurement of platelet aggregation. Total occlusion rates within 240 minutes were 87.5% (7:8), 37.5% (3:8), and 85.7% (6:7) in the control, cilostazol, and ticlopidine groups, respectively. Compared with the control group, the time to total occlusion was significantly prolonged in the cilostazol group, but not in the ticlopidine group. Consistently, platelet aggregation was significantly inhibited only in the cilostazol group. Because ticlopidine increases blood flow in the intact carotid artery before injury to a greater extent than cilostazol, direct antiplatelet action is thought to be responsible for cilostazol's beneficial effect in preventing thrombotic occlusion. These results suggest that cilostazol may be useful for the inhibition of the thrombus formation in the carotid artery and for the prevention of cerebral ischemic events.

Autosomal dominant familial hypoparathyroidism and sensorineural deafness without renal dysplasia.

OBJECTIVE: A family is described which has a unique combination of autosomal dominant hypoparathyroidism and sensorineural deafness without renal dysplasia. CASE REPORT: The proband was a male infant aged 1 month with episodes of seizures for 20 days. He was born at 35 weeks' gestation without asphyxia, weighing 2040 g. His initial calcium, phosphorus and percentage of tubular reabsorption of phosphorus were 6.8 mg/dl (normal range 8.5-10.5 mg/dl), 8.9 mg/dl (normal range 5.5-7.4 mg/dl) and 96.8% (normal range 85-95%) respectively. He had normal values for serum parathyroid hormone (PTH) and 25-hydroxyvitamin D. No abnormalities were found by renal imaging and a routine renal function study. He showed a brisk plasma cAMP increase in response to human PTH-(1-34) infusion. He had normal karyotype 46, XY, without a microdeletion in chromosome 22q11.2 by an in situ hybridization method. Five family members were affected with hypoparathyroidism with sensorineural deafness with autosomal dominant transmission. The study of calcium-sensing receptor and preproPTH gene showed a normal DNA sequence. CONCLUSION: The combination of familial hypoparathyroidism with sensorineural deafness without renal dysplasia is novel and the cause may be distinct from previously reported familial hypoparathyroidism with sensorineural deafness and renal dysplasia.

Association of interleukin 6 release from endothelial cells and pulmonary hypertension in SLE.

OBJECTIVE: To investigate how sera from 37 patients with systemic lupus erythematosus (SLE) stimulate interleukin (IL) 6 release from IL-1beta pretreated endothelial cells and compare these effects to those of sera from 16 normal controls. METHODS: Endothelial cells pretreated 18 h with IL-1beta (5 U/ml) were incubated 2 h with sera diluted 10-fold with phosphate buffered saline (PBS). IL-6 concentrations in endothelial culture supernatants collected after incubation were measured by ELISA. RESULTS: Compared with PBS, sera from controls and 24 patients with SLE suppressed IL-6 release from IL-1beta pretreated cells. However, sera from 13 patients with SLE augmented IL-6 release. Of note, sera from 5 patients with pulmonary hypertension induced the highest level of IL-6 release. IgG from control sera suppressed IL-6 release, whereas F(ab')2 did not. Both IgG and F(ab')2 from the sera of patients with SLE with pulmonary hypertension augmented IL-6 release from IL-1beta pretreated cells. CONCLUSION: IgG antiendothelial cell antibodies from patients with SLE may be associated with the pathogenesis of SLE and pulmonary hypertension.

Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita.

The DAX-1 [DSS (dosage-sensitive sex)-AHC critical region in the X, gene 1] gene has been reported to be responsible for X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism. However, the function and structure of the DAX-1 protein have not been characterized. In this study, molecular analysis of the DAX-1 gene from 6 patients with AHC, including 2 siblings, identified 5 novel mutations with 3 nonsense mutations and 2 frameshift mutations. Case 1 had a nonsense mutation at position 395 (Q395X). Cases 2 and 3, who were siblings, had a nonsense mutation at position 91 (Y91X). Case 4 had a 2-base deletion (AT) at nucleotides 1610 and 1611 and a 1-base insertion (G) resulting in a premature stop codon at position 462 (1610-1611 del AT ins G). Case 5 had a nonsense mutation at position 271 (Y271X). Case 6 had a 1-base deletion (C) at nucleotide 1169, which induced a frame shift and a premature stop codon at position 371 (1169 del C). All mutated DAX-1 proteins had truncated C-terminal domains. In addition, reverse transcription-PCR and direct sequencing characterized the mutant messenger ribonucleic acid in testis from case 1. Our results suggest that these 5 novel mutations are responsible for X-linked AHC and that the C-terminus of the DAX-1 protein, especially the terminal 11 amino acids, is necessary for normal adrenal cortical embryogenesis.

DNA analyses of XX and XX-hypospadiac males.

Fourteen 46,XX "males" were analyzed by Southern blot hybridization with seventeen different Y chromosome-derived DNA probes and by the polymerase chain reaction for an additional two sites on the short arm of Y. Eight 46,XX males possessed various segments of the short arm of the Y chromosome, including the sex determining region. The detected segments ranged from the two most distal loci to nearly the entire length of the short arm, viz., 10 out of 11 loci. None of the eight patients had hypospadia. Five out of the six remaining cases had hypospadia and no Y sequence was detected, suggesting the presence of a causative difference between hypospadiac and non-hypospadiac groups.

[Transverse ectopia of the testis. A case report].

A case of transverse ectopia of the right testis with left inguinal hernia is reported. A one-year-old-boy was admitted to our hospital with swelling of the left scrotal contents and right undescended testis. At operation, two testes were situated on the left side, one in the left scrotum and another in the left inguinal canal. Right transseptal orchiopexy was performed. Including our case, we discovered 73 cases of transverse ectopia of the testes in the Japanese literature. A brief discussion was made about the disease.

[A case of angiomyolipoma originating from polycystic kidney with horseshoe kidney].

A case of renal angiomyolipoma originating from polycystic kidney with horseshoe kidney is reported. A 32-year-old woman visited our hospital with the complaint of proteinuria. with computerized tomographic scan and further examinations the patient was diagnosed as having renal angiomyolipoma with tuberous sclerosis. The tumor originated from a polycystic horseshoe kidney. Three weeks later, she complained of right flank pain and was diagnosed with spontaneous rupture of the angiomyolipoma. Right heminephrectomy was performed and histological examination confirmed the preoperative diagnosis. Some discussion is made on the characteristics and treatment of renal angiomyolipoma, and the statistics on renal diseases with tuberous sclerosis in Japan are presented.

[A case of vesical malacoplakia].

A 44-year-old woman was admitted to our hospital, complaining of terminal hematuria. On cystoscopy four yellow and soft nodular masses were observed in the bladder, one of which had central ulceration. TUR was performed for these masses. Histological examination revealed that they were vesical malacoplakia. The masses consisted of aggregates of macrophages with abundant cytoplasma in which typical Michaelis-Gutmann bodies were demonstrated by light and electron microscopies.