Cholestanol induces apoptosis of cerebellar neuronal cells

Cerebrotendinous xanthomatosis (CTX) is a hereditary lipid storage disease characterized by hyper-cholestanolemia, cerebellar ataxia, xanthoma, and cataract. We hypothesized that cholestanol in serum of CTX patients might induce neuronal cell death in the cerebellum and eventually lead to cerebellar ataxia. To gain support for this hypothesis we developed hyper-cholestanolemia rats by feeding cholestanol. Neuronal cells, especially Purkinje cells in the cerebellum were stained by Sudan black B only in the cholestanol-fed rats, indicating the deposit of cholestanol in cerebellum. To examine effects of cholestanol in vitro, cerebellar neuronal cells were cultured with cholestanol. The cholestanol concentration increased and the viability decreased in cells cultured with cholestanol. Apoptosis was evident in cells cultured with cholestanol more frequently than in control cells, determined using the terminal deoxynucleotidyl transferase (TdT) dUTP nick end-labeling (TUNEL) method. As activities of interleukin-1beta-converting enzyme (ICE) and CPP32 protease were increased in cells cultured with cholestanol, all these data taken together suggest that cholestanol induced apoptosis of cerebellar neuronal cells. Our observations may explain the mechanism of cerebellar ataxia of CTX patients.     

Atresia ani with diphallus and separate scrota in a calf: a case report

Atresia ani, a common genetic defect in animals, is often accompanied by urogenital defects in calves. This paper reports a case of atresia ani with diphallus and separate scrota in a calf. The calf was born with atresia ani; surgery (to open the anus) was performed 3 days after birth. No urogenital abnormalities were noticed until 4 months after birth. At that time, two separate scrota (each containing a testis) and a sac-like structure in the middle of two scrota, were visible. The gait was abnormal, with abduction of the hind limbs while walking. Additionally, the hind legs appeared wider than usual at the hip joints. Two weeks later, two peni (diphallia) was observed, each in a separate preputial sheath. The calf had a normal karyotype on cytogenetic examination. Plasma concentrations of testosterone at 5.5, 6, and 7 months of age were 3.5, 1.9, and 1.7 ng/ml, respectively. At necropsy (7 months of age), the prepuce was thick and the glans of the right penis was adhered to the prepuce. The left penis did not have a urethra or retractor penis muscles. The sac-like structure in the middle of the two scrota contained the urinary bladder and a loop of small intestine. The pubic bone had failed to fuse at the pelvic symphysis. In conclusion, this is the first reported case of atresia ani with diphallus, separate scrota, and pubic bone separation in a calf.     

Luteal function and conception in lactating cows and some factors influencing luteal function after first insemination

The objective of this study was to investigate the types and incidence of luteal sub-function in lactating cows after artificial insemination (AI) and their relationship with pregnancy, and to clarify the relationship between luteal function and parity, body condition score (BCS), milk yield, and dietary intake. In 19 cows, milk samples were collected daily from AI to confirmation of pregnancy. Milk progesterone concentrations were determined by EIA. Based on peak progesterone concentration and the day of onset of luteal phase, 15 of 30 progesterone profiles (50%) were normal, with progesterone concentration reaching 1.0 ng/ml within 5 days after insemination and > or =2.0 ng/ml thereafter. In addition, 6 (20%) were insufficient, (progesterone concentration remained < 2.0 ng/ml), 5 (17%) were delayed (progesterone reached 1.0 ng/ml after 5 days), 2 (7%) were both delayed and insufficient, one (3%) was short (progesterone >1.0 ng/ml for only 7 days), and one (3%) remained basal. Cows with a normal profile had a higher (P < 0.05) pregnancy rate than those with an abnormal profile (87% versus 33%, respectively). The amount of progesterone secreted in milk after first AI, as indicated by progesterone area under curve (AUC), was negatively correlated with milk yield (r = -0.83, P < 0.01), dry matter intake (r = -0.81, P < 0.05), total digestible nutrients (r = -0.82, P< 0.05), and digestible crude protein (r = -0.79, P <0.05). Cows that produced more milk and consumed more dry matter had less progesterone during the luteal phase. In conclusion, abnormal luteal function was associated with reduced pregnancy rates and high milk production and increased dietary intake during breeding were associated with reduced progesterone concentrations.     

A two-dimensional mathematical model of percutaneous drug absorption

Background  

When a drug is applied on the skin surface, the concentration of the drug accumulated in the skin and the amount of the drug eliminated into the blood vessel depend on the value of a parameter, r. The values of r depend on the amount of diffusion and the normalized skin-capillary clearence. It is defined as the ratio of the steady-state drug concentration at the skin-capillary boundary to that at the skin-surface in one-dimensional models. The present paper studies the effect of the parameter values, when the region of contact of the skin with the drug, is a line segment on the skin surface.     

Solution properties of gellan gum: change in chain stiffness between single- and double-stranded chains

Nine samples of gellan gum in the sodium form, ranging in weight-average molar mass from 3.47 x 10(4) to 1.15 x 10(5) at 40 degrees C, were investigated by static and dynamic light scattering and viscometry in 25 mM aqueous NaCl both at 40 and at 25 degrees C. The ratios of the molar mass at 25 degrees C (in the ordered state) to that at 40 degrees C (in the disordered state) were in the range of 1.99 to 2.07, supporting the scheme of the conformational transition of gellan gum between a disassociated single chain and an associated chain composed of two molecules. Focusing on the effects of polydispersity, the intrinsic viscosities, radii of gyration, and hydrodynamic radii were analyzed on the basis of unperturbed wormlike chain models. The persistence lengths were evaluated as 9.4 nm at 40 degrees C and 98 nm at 25 degrees C.     

Efficient asymmetric syntheses, determination of absolute configurations and biological activities of 1-[4,4-bis(4-fluorophenyl)butyl]-4-[2-hydroxy-3-(phenylamino)propyl]piperazine as a novel potent dopamine uptake inhibitor in the central nervous system

An efficient asymmetric synthesis of the chiral N-(3-chloro-2-hydroxypropyl)anilines (2a and 2b) was achieved through the regioselective ring-opening reaction of chiral epichlorohydrin with aniline. This was applied to an asymmetric synthesis of the enantiomers of 1-[4,4-bis(4-fluorophenyl)butyl]-4-[2-hydroxy-3-(phenylamino)propyl]piperazine 1 as a novel potent dopamine uptake inhibitor. Both enantiomers as trihydrochlorides, 4a.3HCl and 4b.3HCl, could be synthesized in good total yields and optical purities of 100% ee in three steps synthesis, respectively. The absolute configurations of 4a.3HCl and 4b.3HCl were determined using the modified Mosher's method with the related compounds, the intermediates (2a and 2b) and the free bases (4a and 4b). The analytical results indicated that 4a.3HCl and 4b.3HCl have the (S)- and (R)-configuration, respectively, and a series of reactions to provide them proceeded without the apparent influence on the stereochemistry at the chiral centers. In in vitro pharmacological evaluations, 4a.3HCl and 4b.3HCl showed potent dopamine transporter binding affinities, high dopamine, moderate serotonin, and weak norepinephrine uptake inhibitory activities, and 4a.3HCl exhibited a more potent and selective dopamine uptake inhibition over the serotonin or norepinephrine uptake inhibition as compared with 4b.3HCl. An ex vivo evaluation revealed that the oral administrations of both enantiomers at a dose of 30 mg/kg in rats displayed apparent dopamine uptake inhibitory activities and 4a.3HCl had a stronger tendency to inhibit dopamine uptake compared with 4b.3HCl.     

Piericidins C5 and C6: new 4-pyridinol compounds produced by Streptomyces sp. and Nocardioides sp

Piericidins C5 (1) and C6 (2), two new members of the piericidin family, were isolated from a Streptomyces sp. and a Nocardioides sp., together with known piericidins C1 (3), C2 (4), C3 (5), C4 (6), D1 (7), and A3 (8). The structures were determined on the basis of their spectroscopic data. Both new compounds inhibited cell division of fertilized starfish (Asterina pectinifera) eggs at the minimum inhibitory concentration of 0.09 microg/mL.     

Cutting edge: a potent adjuvant effect of ligand to receptor activator of NF-kappa B gene for inducing antigen-specific CD8+ T cell response by DNA and viral vector vaccination

The ligand to receptor activator of NF-kappaB (RANK-L)/RANK interaction has been implicated in CD40 ligand/CD40-independent T cell priming by dendritic cells. In this report, we show that the coadministration of the RANK-L gene with a Trypanosoma cruzi gene markedly enhances the induction of Trypanosoma Ag-specific CD8(+) T cells and improves the DNA vaccine efficacy. A similarly potent adjuvant effect of the RANK-L gene on the induction of Ag-specific CD8(+) T cells was also observed when recombinant influenza virus expressing murine malaria Ag was used as an immunogen. In contrast, the coadministration of the CD40L gene was not effective in these systems. Our results demonstrated, for the first time, the potent immunostimulatory effect of the RANK-L gene to improve the CD8(+) T cell-mediated immunity against infectious agents.     

A human case of gnathostomiasis nipponica confirmed indirectly by finding infective larvae in leftover largemouth bass meat

A human case of creeping eruption due to Gnathostoma nipponicum was confirmed indirectly by finding infective advanced third-stage larvae in leftover largemouth bass meat. This is the first report indicating that the largemouth bass (Micropterus salmoides) serves as a source of G. nipponicum infection in humans.