Effects of testosterone, and testosterone plus estrogen, in the castrated rat ventral prostate--histopathological and immunocytochemical studies.

The effects of testosterone (T) and 17 beta-estradiol (E2) on the prostate of castrated rats were investigated by histopathological and immunocytochemical procedures. A significant increase in prostatic weight occurred after 6 weeks treatment with T alone and in combination with E2. The greatest increase in prostatic weight occurred after the administration of T plus E2. Histopathologically, glandular hyperplasia of the prostate was noted, and the number of bromodeoxyuridine (BrdU)-positive cells showed a significant increase over that induced by testosterone alone.     

Inhibitory influence of a new steroidal anti-androgen, TZP-4238, on prostatic hyperplasia in the beagle dog.

The effect of a synthetic steroidal anti-androgen, TZP-4238, on spontaneous benign prostatic hyperplasia (BPH) in dogs was investigated. Old male beagle dogs (5-9 years old) were divided into three experimental groups. Group 1 consisted of BPH controls. Groups 2 and 3 received TZP-4238 0.1 mg/kg/day and chlormadinone acetate (CMA) 0.3 mg/kg/day p.o., respectively, for 5 months. In group 1, glandular hyperplasia of the prostate was clearly detected. In contrast, TZP-4238 (Group 2) or CMA (Group 3) produced marked atrophy of the glandular epithelium. In addition, a histopathological study showed that TZP-4238 or CMA medication for 5 months exerted no effect on the testes and the pituitary luteinizing hormone (LH) cells. Therefore, it is suggested that TZP-4238 (0.1 mg/kg) or CMA (0.3 mg/kg) causes regression of spontaneous canine BPH without any histopathological effects on the testes and pituitary LH cells. However, slightly decreased serum testosterone levels were found in TZP-4238-treated animals, due apparently to a direct and/or indirect effect on the testes. Thus, it is suggested that a marginal antigonadotrophic effect cannot be excluded. It is concluded that TZP-4238 is a potent anti-androgen for the treatment of spontaneous canine BPH, without any negative influence on the function of the testes and the pituitary LH cells.     

Effect of anti-androgen (TZP-4238) on steroid-induced canine prostatic hyperplasia. Light and electron microscopic investigations.

The effect of a synthetic steroidal anti-androgen, TZP-4238, on steroid-induced canine prostatic hyperplasia was studied by light and electron microscopy. Male beagle dogs (1-2 years old) were divided into four experimental groups. Group 1 consisted of intact controls. The other animals were castrated. The castrated animals were treated for 25 weeks with 1) 5 alpha-androstane-3 alpha, 17 beta-diol (A-diol) plus 17 beta-estradiol (E2) (Group 2), 2) A-diol plus E2 + TZP-4238 0.5 mg/kg (Group 3) and 3) A-diol plus E2 + chlormadinone acetate (CMA) 2.5 mg/kg (Group 4). TZP-4238 and CMA were administered orally for 21 weeks after 4 weeks treatment with A-diol plus E2. In group 2, glandular hyperplasia of the prostate was clearly noted. In contrast, combined treatment with TZP-4238 (Group 3) or CMA (Group 4) produced marked atrophy of the glandular epithelium. Loss of secretory and metabolic activities was confirmed by ultrastructural investigations. Our data indicate that TZP-4238 is a potent anti-androgen for the prevention of canine prostatic hyperplasia in the steroid-induced benign prostatic hyperplasia (BPH) model.     

Effect of Enteral Nutrition on In-hospital Infection and Hospital Expense in Stroke Patients: A Retrospective Assessment

Infection is a common complication of stroke and is associated with unfavorable outcomes. Although nutritional intervention reduces the risk of postoperative infection, the impact of specific nutritional products remains unclear. From a hospital management perspective, we aimed to determine whether the provision of specific types of enteral nutrition in acute stroke patients affects infection control and hospital costs. In all, 45 acute hemorrhagic stroke patients receiving enteral nutrition in a single center (April 2017–March 2019) were retrospectively assessed. Patients were divided into two groups according to nutritional interventions: the 1.0-group with general nutrition (1.0 kcal/mL) (24 patients) and the 1.5+α-group with an initial high-protein, whey peptide-digested liquid diet (1.5 kcal/mL), followed by a highly fermentable fiber-containing liquid diet (1.5 kcal/mL initiated after 4 days) (21 patients). Changes in body mass index (BMI), duration of antibiotic use, incidence of postoperative infection, and medical cost were evaluated. Baseline patient characteristics were similar between groups. The mean BMI change was lower in the 1.5+α-group than in the 1.0-group, and the mean duration of antibiotic use throughout hospitalization was 12.8 and 18.3 days, respectively. Antibiotic use in the 1.5+α-group was lesser than that in Japanese patients from other hospitals. The incidence of postoperative infections was lower in the 1.5+α-group. Injection costs for the 1.5+α group (615 USD/patient) were lower than those for the 1.0-group. Enteral nutrition provided to acute stroke patients reduced the risk of hospital infection and medical costs.     

Advantage of semi-ionic bonding in fluorine-doped carbon materials for the oxygen evolution reaction in alkaline media

Metal-free carbonaceous catalysts have potential applications for oxygen evolution reaction (OER) devices because of their low-cost and abundant supply. We report that fluorine-doped carbon black is an active catalyst for OER. Fluorine-doped carbon black (F-KB) is simply synthesized by the pyrolysis of KETJENBLACK (KB) as carbon substrate with Nafion as fluorine precursor. As a result, the OER activity of F-KB is significantly higher than that of pristine KB in alkaline media. The OER catalytic activity of F-KB is found to be dependent on the quantity and characteristics of carbon-fluorine bonding (C–F) which can be controlled by the pyrolysis temperature. It is further found that the OER activity depends on the quantity of semi-ionic C–F bonds, but not covalent C–F bonds. This result proves the importance of carbon atoms with semi-ionic C–F bonds as the active sites for OER.

Fluorine-doped carbon has a higher electrocatalytic oxygen evolution activity than pristine carbon black in alkaline media. The activity of oxygen evolution and characteristics of carbon to fluorine bond are controlled by pyrolysis temperature of Nafion.     

Effects of dextran sulfates on the acute infection and growth stages of Toxoplasma gondii

Toxoplasma gondii is one of the most prevalent parasites, causing toxoplasmosis in various warm-blooded animals, including humans. Because of the broad range of hosts susceptible to T. gondii, it had been postulated that a universal component of the host cell surface, such as glycosaminoglycans (GAGs), may act as a receptor for T. gondii infection. Carruthers et al. (Infect Immun 68:4005–4011, 2000) showed that soluble GAGs have also been shown to disrupt parasite binding to human fibroblasts. Therefore, we investigated the inhibitory effect of GAGs and their analogue dextran sulfate (DS) on T. gondii infection. For up to 24 h of incubation after inoculation of T. gondii, the inhibitory effect of GAGs on T. gondii infection and growth inside the host cell was weak. In contrast, DS markedly inhibited T. gondii infection. Moreover, low molecular weight DS particularly slowed the growth of T. gondii inside host cells. DS10 (dextran sulfate MW 10 kDa) was the most effective agent in these in vitro experiments and was therefore tested for its inhibitory effects in animal experiments; infection inhibition by DS10 was confirmed under these in vivo conditions. In this report, we showed that DSs, especially DS10, have the potential of a new type of drug for toxoplasmosis.     

Ricolinostat (ACY‐1215) induced inhibition of aggresome formation accelerates carfilzomib‐induced multiple myeloma cell death

Proteasome inhibition induces the accumulation of aggregated misfolded/ubiquitinated proteins in the aggresome; conversely, histone deacetylase 6 (HDAC6) inhibition blocks aggresome formation. Although this rationale has been the basis of proteasome inhibitor (PI) and HDAC6 inhibitor combination studies, the role of disruption of aggresome formation by HDAC6 inhibition has not yet been studied in multiple myeloma (MM). The present study aimed to evaluate the impact of carfilzomib (CFZ) in combination with a selective HDAC6 inhibitor (ricolinostat) in MM cells with respect to the aggresome‐proteolysis pathway. We observed that combination treatment of CFZ with ricolinostat triggered synergistic anti‐MM effects, even in bortezomib‐resistant cells. Immunofluorescent staining showed that CFZ increased the accumulation of ubiquitinated proteins and protein aggregates in the cytoplasm, as well as the engulfment of aggregated ubiquitinated proteins by autophagosomes, which was blocked by ricolinostat. Electron microscopy imaging showed increased autophagy triggered by CFZ, which was inhibited by the addition of ACY‐1215. Finally, an in vivo mouse xenograft study confirmed a decrease in tumour volume, associated with apoptosis, following treatment with CFZ in combination with ricolinostat. Our results suggest that ricolinostat inhibits aggresome formation, caused by CFZ‐induced inhibition of the proteasome pathway, resulting in enhanced apoptosis in MM cells.