Five‐year efficacy of finasteride in 801 Japanese men with androgenetic alopecia

Finasteride is standard medical treatment for androgenetic alopecia; however, no large studies with 5 years or more of follow up have been performed in Japan. The authors followed Japanese men with androgenetic alopecia treated with finasteride for 5 years to evaluate long‐term treatment efficacy. Of 903 men treated with finasteride (1 mg/day), 801 patients were evaluated over 5 years by modified global photographic assessment. Although the proportion of improvement was high (99.4%), modified global photographic assessment scores after 5 years of treatment were lower in patients with more advanced disease as measured by the modified Norwood–Hamilton scale. After separating patients into “sufficient” and “insufficient” efficacy groups according to the modified global photographic assessment score after 5 years (scores ≥6 and <6, respectively), multivariate analysis showed that independent risk factors of insufficient efficacy were age at start of treatment of 40 years or more (P = 0.021) and classification on the modified Norwood–Hamilton scale (P < 0.001), whereas presence of stress at start of treatment was a negative predictor (P = 0.025). In conclusion, continuous finasteride treatment for 5 years improved androgenetic alopecia with sustained effect among Japanese. Younger age and less advanced disease at start of treatment were the key predictors of higher finasteride efficacy.     

A case of diaphragmatic hernia incarceration after a heart transplant operation

We report a case of a diaphragmatic hernia after a heart transplant operation. A 43-year-old woman, who underwent orthotropic heart transplantation for hypertrophic cadiomyopathy two year earlier, presented with vomiting and epigastric pain. A computed tomography scan showed that the stomach and transverse colon were dislocated in the left thoracic cavity. We diagnosed left diaphragmatic hernia incarceration and performed laparoscopic repair of the diaphragmatic hernia. A 12 × 8 cm diaphragmatic defect was found intraoperatively on the ventrolateral aspect of the left diaphragm, and the stomach with volvulus had herniated into the thorax through the defect. The hernia was considered to be iatrogenic. The diaphragmatic defect was large, and the diaphragm was thinning. We closed the defect by mesh repair. Laparoscopic mesh repair of the diaphragmatic hernia could be performed safely and with minimal invasiveness.     

Activation of protein kinase C and nicotinamide adenine dinucleotide phosphate oxidase in leukocytes of spontaneously hypertensive rats.

The involvement of oxidative stress in polymorphonuclear leukocytes (PMN) in the pathogenesis of hypertension remains to be elucidated. We analyzed the generation of reactive oxygen species (ROS) by the circulating and peritoneally infiltrating PMN from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Flow cytometric analysis revealed that ROS generation by PMN from SHR was higher than that from WKY before (at 6 weeks of age) and after (at 16 weeks of age) the onset of hypertension. In vivo, ROS generation by PMN from SHR, but not that by PMN from WKY, was significantly suppressed by 10-week treatment with 50 mg/kg/day carvedilol, and this treatment did not affect blood pressure. Western blotting analysis revealed that protein kinase C alpha (PKCalpha), but not PKCbetaI or betaII, was activated more strongly in PMN from SHR than in PMN from WKY. Furthermore, expression of p47phox of nicotinamide adenine dinucleotide phosphate oxidase, but not of p67phox, in PMN from SHR was higher than that in PMN from WKY. These results suggest that ROS generation by PMN is principally enhanced in SHR through activation of PKCalpha and p47phox.     

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.     

Effects of anthocyanidin derivative (HK-008) on relaxation in rat perfused mesenterial bed.

Anthocyanins, which are responsible for a variety of bright colors (including red, blue, and purple) in fruits, vegetables, and flowers, are consumed as dietary polyphenols. Anthocyanin-containing fruits are thought to decrease coronary heart disease and are used in anti-diabetic preparations. Diabetes is associated with a variety of cardiovascular complications that may be mediated by endothelial dysfunction, and so this study was designed mainly to characterize the influence of a synthesized anthocyanidin derivative (HK-008) over acetylcholine (ACh)-induced relaxation in mesenteric arterial beds isolated from rats. In a glucose-tolerance test in intact rats, HK-008 (30 mg/kg) reduced the glucose level as effectively as the same dose of glibenclamide. The aortic relaxation induced by pinacidil (an ATP-sensitive potassium channel opener) was greatly inhibited by glibenclamide (10 microM), and also significantly inhibited by HK-008 (10 microM). Interestingly, the ACh-induced relaxation in the perfused, preconstricted mesenteric arterial bed was significantly enhanced by HK-008 (10 microM), and this enhancement was significantly attenuated by indomethacin (10 microM). The ACh-induced mesenteric relaxation was impaired by an increase in oxidative stress, viz. superoxide-generating treatment [xanthine oxidase (XO; 0.1 U/ml) plus hypoxanthine (HX; 10 microM)]. However, this impairment was strongly suppressed by HK-008 (10 microM). These results suggest that HK-008 increases endothelium-induced relaxation by suppressing oxidative stress or modulating prostanoids signaling. This compound may therefore be useful against certain cardiovascular disorders.     

Experimental studies of photo radiation therapy on neuroblastoma

A combination of Photo Radiation Therapy (PRT) using Argon-Dye Laser with hematoporphyrin derivatives (HpD) was used experimentally on a cytogenetically highly malignant neuroblastoma xenograft, which exhibited a homogeneously staining region and caused DNA amplifications in chromosomes. The tumor tissue was treated with 500 joules/cm2 of laser. The dosage of HpD was 50 mg per kg body weight. Necrosis of over 50% of the tumor was observed in half the specimens. Swollen cytoplasmic organelles and ruptured cell and nuclear membranes were observed by electron microscopy after PRT. PRT may be used with other treatment modalities for the removal of residual and metastatic tumors.     

Effects of anti-asthmatic drugs on human eosinophil chemotaxis]

To evaluate the acute effects of anti-asthmatic drugs in vitro, we examined the modulation of various anti-asthmatic drugs in therapeutic concentrations on PAF-induced human eosinophil chemotaxis. Aminophylline (20 micrograms/ml) and Isoproterenol (10 nM) inhibited PAF (3 X 10(-8) M)-induced eosinophil chemotaxis nearly 30%, whereas no inhibitory effects were observed by Dexamethasone (0.1 microM), Tranilast, Ketotifen or Azelastine. Aminophylline (20 micrograms/ml) also inhibited LTB4 (3 X 10(-8) M)-induced eosinophil chemotaxis nearly 30%, whereas it did not inhibit chemotaxis induced by zymosan (5 mg/ml)-activated serum. These results indicate that anti-asthmatic drugs except for aminophylline and isoproterenol, when used acutely in therapeutic concentrations, have no striking inhibitory effects on PAF-induced eosinophil chemotaxis. These results further suggest the possibility that there are different mechanisms in eosinophil chemotaxis induced by PAF, LTB4 or by C5a.     

Isolation, purification, and characterization of an acidic protein in the cerebrospinal fluid of central nervous system disease.

Proteins from 21 cerebrospinal fluid (CSF) samples (14 derived from neurological cases and 7 from normal individuals) and 15 serum samples (11 from neurological cases and 4 from normal individuals) were analyzed by two-dimensional electrophoresis. Protein mapping revealed a very acidic protein (Ac-P) at about pH 3.5 in the 71% of CSF samples from neurological cases. However, no serum sample contained Ac-P. Ac-P was isolated and purified, and determined to be a glycoprotein containing a large amount of carbohydrate, with molecular weight 42,000 and isoelectric point 2.7-3.3. The amino acid composition of Ac-P was consistent with alpha 1-acid glycoprotein (AGP), and Ac-P was responsive to a commercial anti-AGP antiserum in the radial immunodiffusion test. The known polymorphism of AGP suggests some differences in physicochemical properties such as molecular weight and isoelectric point between AGP in serum and in CSF. Quantitative analysis of Ac-P (AGP) and total protein levels in CSF showed a partial interdependence. Ac-P may be a useful marker for detecting a pathological conditions of the central nervous system.