Dietary Cystine Ameliorates Defects in Spermatogenesis via Testosterone Production Induced by Protein Deficiency and Darkness in Rats.

Nutrition and light-dark cycle influence rat testicular development. With 9% casein diet (low protein diet) under normal 12 h-12 h lighting cycles (9P), juvenile rat testes undergo normal growth. On the other hand, a low protein diet with constant darkness (D9P) results in a growth arrest of rat testes. Supplementation of cystine to the low protein diet under constant darkness (D9PC) had a tendency to increase testes weight, suggesting an improvement in growth suppression. Whether the growth suppression of testes in D9P is associated with suppression of spermatogenesis has not yet been shown. We aimed to determine the effect of a low protein diet and constant darkness with or without dietary cystine in testes using a histological technique. In the histological assessment, D9P testes showed a decreased number of seminiferous tubules with elongated spermatids, indicating a functional testicular defect in this group. However, cystine supplementation resulted in enhanced spermatogenesis versus control animals (D9PC vs. D9P) implying the importance of cystine to testicular development in this condition. Furthermore, serum testosterone concentration was increased in D9PC suggesting contribution of testosterone to ameliorate spermatogenesis. From these results, we conclude that cystine supplementation to a low protein diet under constant darkness promoted an increase in testosterone which in turn benefitted spermatogenesis.

Cerebral Insufficiency Caused by Diazoxide in a Premature Neonate with Congenital Hyperinsulinism.

Diazoxide is a peripheral vasodilator that has been used for intravenous treatment of hypertensive emergencies. However, it is currently used mainly for hyperinsulinemic hypoglycemia in lower dose orally, and its major side effects are edema and pulmonary hypertension. Herein, we report the first association between periventricular leukomalacia (PVL) and intractable hypotension due to diazoxide. A Japanese female premature infant showed hypoglycemia concomitant with hyperinsulinemia. She was diagnosed with congenital hyperinsulinism, and oral diazoxide was started. Six days after starting diazoxide, she suddenly showed peripheral coldness, oliguria, and severe hypotension. The hypotension was refractory to general vasopressor therapies and persisted even after the discontinuation of diazoxide. Cranial echography showed periventricular echodensities followed by cystic PVL. Low-dose vasopressin effectively treated the hypotension. This single case reminds us the serious adverse events of diazoxide that have been forgotten, especially in premature neonates.

Two infants with tuberculid associated with Kawasaki disease.

Bacille de Calmette et Guerin (BCG) is the only licensed tuberculosis vaccine to prevent severe tuberculosis. The adverse events of BCG vaccination, including local reactions, lymphadenitis, osteomyelitis, tuberculid, and disseminated infection, have been reported. Two infants presented erythema at the inoculation site of BCG after the resolution of Kawasaki disease (KD). They received BCG vaccination 1 week and 6 weeks before the KD onset, respectively. Intravenous immunoglobulin improved the KD activity, however the skin rash of BCG inoculation site extended to the face and extremities days 24 and 10 after the KD onset, respectively. Both bacteriological study and interferon-γ release assay were negative for Mycobacterium tuberculosis infection. These patients were diagnosed as having tuberculid after KD. The skin lesions gradually disappeared without antibiotic therapy over 2 months. The development of tuberculid in these patients might be associated with the remnant immune activation of KD.

Coffee reduces SULT1E1 expression in human colon carcinoma Caco-2 cells.

Recent epidemiological studies have shown that moderate coffee consumption is associated with a lower risk of certain types of cancers, particularly colon cancer in postmenopausal women. To elucidate the molecular basis for the preventive action of coffee, we investigated the effect of coffee on estrogen sulfotransferase (SULT) because sulfation is the major pathway involved in the inactivation of estrogens. We found that coffee reduced SULT1E1 gene expression in human colon carcinoma Caco-2 cells. Treatment with 2.5% (v/v) coffee for 24 h resulted in a 60% reduction of the expression of the SULT1E1 gene in Caco-2 cells. Corresponding to reduced SULT1E1 gene expression, cytosolic estrogen SULT activity toward E(2) (20 nM) decreased by 25%. In addition, an accumulation of E(2) sulfates in the medium, which reflects cellular activity of estrogen SULT, decreased after the cells were treated with coffee. Major bioactive constituents in coffee such as caffeine, chlorogenic acid and caffeic acid did not show any effect. The inhibitory activity was extractable by using ethyl acetate. We also found that the inhibitory activity was produced by roasting the coffee beans. Mithramycin, an inhibitor of the transcription factor stimulating protein 1 (Sp1), was able to restore coffee-reduced SULT1E1 gene expression. Our data suggest that daily coffee consumption may reduce estrogen SULT activity, thereby enhancing estrogenic activity in the colon.

Fertility restoration by Ifr1 in rice with BT-type cytoplasmic male sterility is associated with a reduced level, but not processing, of atp6-orf79 co-transcribed RNA.

BT-type cytoplasmic male sterility (CMS) in rice is associated with accumulation of unprocessed dicistronic RNA containing a duplicated atp6 (B-atp6) and an unusual open reading frame, orf79, encoding a cytotoxic peptide in mitochondria. The male-sterile state of BT-type CMS is stably maintained by backcrossing the plants with line Taichung 65 (T65) that has no restorer gene and is completely suppressed by the presence of the Rf1 gene through the processing of B-atp6-orf79 RNA. A variant of the T65 line, T65(T), has a weak restoration function conferred by the Ifr1 gene, which is genetically independent of the Rf1 gene. However, not much is known about the mechanism(s). In a study to examine whether the mechanism involved in fertility restoration by Ifr1 is analogous to restoration mediated by Rf1, the transcript profile of B-atp6-orf79 in male-sterile plants was compared with that in fertility restored plants obtained by crossing male-sterile plants with T65(T). The cellular level of unprocessed B-atp6-orf79 RNA was reduced in the restored plants, but no change in processing efficiency or the quantity of B-atp6-orf79 DNA was detected. These results suggest that Ifr1 restores fertility through reducing either the transcription rate of B-atp6-orf79 or the stability of its primary transcripts, a mechanism distinct from that involved in fertility restoration of BT-type CMS by Rf1.