Renal toxicity induced by folic acid is associated with the enhancement of male reproductive toxicity of di(n-butyl)phthalate in rats

Reproductive effects have been observed in experimental animals treated with di(n-butyl)phthalate (DBP), one of phthalate esters used in soft plastics and a variety of consumer products. In this study, we investigated whether testicular toxicity of DBP is influenced by diminished renal function. To generate an experimental condition reflecting chronic renal disease in man, adult male F344 rats were given five consecutive weekly subcutaneous injections of folic acid at a dose of 300 mg/kg and then a diet containing 1200, 5000, and 20,000 ppm of DBP for 4 weeks. These concentrations roughly correspond to 60, 250, and 1000 mg/kg per day per rat, respectively. Folic acid clearly induced interstitial nephritis accompanied by impairment of renal function. Seminiferous degeneration, diminished spermatogenesis and increase in the number of morphologically abnormal sperm were more prominent in rats given folic acid and then 20,000 ppm DBP as compared to those exposed to DBP alone. These data suggest that DBP-induced male reproductive toxicity can be increased by folic acid-induced renal dysfunction.     

Correlation of Repeated Measurements of Home Blood Pressure on One Occasion and Diagnosis of Hypertension: Study by Measurement over Seven Consecutive Days

In spite of the recent recognition of the usefulness of home blood pressure (BP) measurement, there are no clear guidelines for which measurements should be used for clinical evaluation. Therefore, the present study examined the correlation of repeated measurements of home BP on one occasion and the diagnosis of hypertension (HT) or normotension (NT). Home BP was measured with 700 volunteers aged 20 years or older (468 male and 232 female, mean age 40.6 years) in a sitting position three times each in the morning and evening for seven consecutive days. Excluding the measurements on the first day, the mean values were calculated for the first measurement (group A), second measurement (group B), the mean of the first and second measurements (group C), and the mean of the second and third measurements (group D). The correlation with the frequency of diagnosis of HT (≥135/85 mmHg) and NT (<125/80 mmHg) was studied. Home BP in the morning and evening were both highest in group A (morning: 122.1 ±0.6 (SEM)/75.9 ±0.4 mmHg, evening: 120.4 ±0.6/71.8 ±0.4 mmHg) and lowest in group D (morning: 119.5 ±0.6 / 75.2 ±0.4 mmHg, evening: 117.5 ±0.6/70.6 ±0.4 mmHg). Using morning home BP, HT was diagnosed more often in group A (27.4%) than in group D (24.7%), with a lower frequency of NT diagnosis (55.7% vs. 61.7%; p?=?0.06). With regard to the diagnosis made from evening home BP, HT was diagnosed more often and NT was diagnosed less often in group A (HT/NT: 18.4%/61.4%) than in group D (13.7%/68.0%), with statistical significance (p?=?0.02). In conclusion, when the clinical diagnosis was made from seven-day home BP, the diagnosis of HT was made more frequently and NT diagnosis was made less frequently using the first measurement than the mean of the second and third measurements. This trend was more pronounced when diagnosis was made from evening home BP.     

Hairspray Inhalation-induced Interstitial Pneumonitis Evaluated by a Transbronchial Lung Cryobiopsy

A 60-year-old Japanese woman was admitted to our hospital with a fever and shortness of breath occurring immediately after using hairspray. Chest high-resolution computed tomography (HRCT) showed ground-glass opacities (GGOs) predominantly distributed around the bronchovascular bundles, and a pathological evaluation by a transbronchial lung cryobiopsy (TBLC) revealed fibrotic non-specific interstitial pneumonia (f-NSIP). Her symptoms disappeared without the use of corticosteroids, and GGOs on HRCT improved markedly over time. This case suggests that a pathological evaluation by a TBLC for lung injury due to inhalation pathogen exposure may provide a more accurate diagnosis and a better understanding of the pathology from bronchial to interstitial lesions than transbronchial lung biopsy.     

Clinical reevaluation of the effect of oxybutynin chloride on uninhibited neurogenic and reflex neurogenic bladder

Oxybutynin chloride has been clinically used for the relief of symptoms associated with voiding in patients with uninhibited neurogenic and reflex neurogenic bladder in the USA. The present clinical and urodynamic studies were the first meticulously in patients with uninhibited neurogenic and reflex neurogenic bladder in Japan. A single oral dose of oxybutynin chloride (3 or 6 mg) did not induce any change either in subjective symptoms or in urodynamic studies; however, in the continual administration study, 7 of 9 patients showed an improvement in the symptoms associated with voiding. The drug reduced urinary frequency, urgency and incontinence, and significantly increased the volumes at the first desire to void (FDV) and maximum desire to void (MDV) in cystometry. Furthermore, no serious adverse reactions were observed, and hence the drug seems to be of clinical significance.     

Cryopreservation of cartilage

Summary We have investigated the viability and function of cells in cartilage slices after various methods of preservation, and have examined the viability of cells by measuring the incorporation of Na₂ ³⁵SO₄ at different concentrations, temperatures and times of exposure to cryopreservatives. We have assessed the viability of cells when exposed to prefreezing temperatures, and after preservation at –80° C. The best survival rate was found to be with a concentration of cryopreservatives of approximately 10%, with pre-freeze exposure for four hours at 4° C. In the stage cooling technique, the best initial cooling was at –30° C for 30 minutes, followed by rapid cooling of the cartilage to –80° C. The best survival rate for cryopreserved cartilage in 10% DMSO was, on average, 19% in intact slices and 34% when holes had been made in the slices. Proteoglycan synthesis after thawing appeared normal, and proteoglycan labelled after 48 hours in culture also showed a normal pattern.

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Résumé Nous avons étudié la viabilité et la fonction cellulaire de coupes de cartilage après diverses méthodes de conservation et nous avons évalué la viabilité des cellules en mesurant l'absorption du Na₂ ³⁵SO₄ à différentes concentrations, températures et durées d'exposition aux cryo-préservateurs. Nous avons évalué la viabilité des cellules exposées aux températures de pré-congélation et après conservation à –80° C. Nous avons trouvé que le meilleur pourcentage de survie était obtenu avec une concentration de cryo-préservateurs d'environ 10%, avec une pré-congélation de 4 heures à 4° C. Dans la technique de refroidissement par étapes, le meilleur refroidissement initial est de –30° C pendant 30 minutes, suivi d'un refroidissement rapide du cartilage jusqu'a –80° C. Le meilleur taux de survie pour le cartilage cryo-préservé dans 10% de DMSO a été, en moyenne, de 19% dans les coupes intactes et de 34% quand des perforations ont été pratiquées dans les coupes. La synthèse du protéoglycan après décongélation paraît normale et le protéoglycan marqué, après une culture de 48 heures, s'avère également normal.

     

A neonatal form of glycogen storage disease type IV

We report of an infant with neonatal glycogen storage disease type IV (GSD IV) who was examined for severe hypotonia and cardiomyopathy. On the muscle biopsy there were many fibers with diastase-resistant polyglucosan bodies. Glycogen branching enzyme (GBE1) activity in the muscle was markedly reduced. The infant had a homozygous single nucleotide deletion in the open reading frame of GBE1 gene.     

Disruption of type 5 adenylyl cyclase gene preserves cardiac function against pressure overload

The sympathetic nervous system is designed to respond to stress. Adenylyl cyclase (AC) is the keystone of sympathetic transmission, yet its role in response to acute overload in the heart or in the pathogenesis of heart failure is controversial. We examined the effects of pressure overload, induced by thoracic aortic banding, in mice in which type 5 AC, a major cardiac AC isoform, was disrupted (AC5-/-). Left ventricular weight/tibial length ratio (LVW/TL) was not different between the WT and AC5-/- at baseline and increased progressively and similarly in both groups at 1 and 3 wk after aortic banding. However, LV ejection fraction (LVEF) fell in WT at 3 wk after banding (from 70 +/- 2.8 to 57 +/- 3.9%, P < 0.05), and this decrease was associated with LV dilatation, indicating incipient cardiac failure. In contrast, AC5-/- mice did not exhibit a fall in LVEF from 74 +/- 2.2%. The number of apoptotic myocytes was similar at baseline, but it increased roughly 4-fold in WT at both 1 and 3 wk after banding, and significantly less, P < 0.05, in AC5-/-. Importantly, the increase in apoptosis occurred before the decline in LVEF in WT. The protective mechanism seems to involve Bcl-2, which was up-regulated significantly more in AC5-/- mice with pressure overload. Our findings suggest that limiting type 5 AC plays a protective role in response to pressure overload and the development of heart failure, potentially through limiting the incidence of myocardial apoptosis.     

Nephrotic syndrome and IgA nephropathy in polycystic kidney disease

A 70-year-old man with polycystic kidney disease developed nephrotic syndrome, deteriorating to renal insufficiency. Histological examination revealed IgA nephropathy. With treatment of prednisolone, an angiotensin-converting enzyme inhibitor, and an angiotensin II receptor-blocker, his proteinuria markedly decreased and renal function was stabilized. This case supports the idea that renal biopsy is needed in patients with polycystic kidney disease with nephrotic-range proteinuria, for appropriate treatment and prevention of renal failure.